Stereoselective Synthesis of N-Glycosyl Oxazolines and Evaluation of Their Antiproliferative Activity

During investigation of different approaches towards fluorodeoxy d-pentofuranoses we have found that reaction of the 3-O-p-toluenesulfonyl xylofuranose derivative 3, prepared via diacetonide 1¹⁵ from d-xylose, witha3.5-foldaccess of the complex of KHF₂with dibenzo-18-crown-6 in acetonitrile in the presence of BF₃^.Et₂O resulted in the formation of N-xylofuranosyl oxazoline7 after the basic aqueous work-up of the reaction mixture and chromatography on silica gel. A selective transformation of the xylofuaranose acetonide derivative 3 with the solvent was observed at the 1,2-O-isopropylidene group in the presence of the Lewis acid (6-7.0 equiv) without formation of fluorinated products by a nucleophilic substitution reaction of the 3-O-p-toluenesulfonyloxy group with inorganic fluoride (Scheme 2).However, application of crown ether gave rise to tedious purification of the product by column chromatography. No reaction was observed under treatment of the tosylate 3 with a 3.5-foldaccess of KHF₂ in CH₃CN at rt and only the startingacetonide was recovered unchanged. Further, it was shown that the oxazoline 7 can be prepared from the acetonide derivative 3 in a high 98% yield using BF₃^.Et₂O/KHF₂ in CH₃CN without column chromatography on silica gel (Scheme 2) as compared to the previous findings reported earlier ¹⁶.

Scheme 2.Synthetic study of N-glycosyl oxazolines from sugar acetonides

In the course of present comprehensive study, conversions of various protected d-pentofuranose and -hexofuranose acetonides with nitriles to glycosyl oxazoline derivatives were explored under BF₃^.Et₂O/KHF₂ reaction conditions at room temperature (Scheme 2 and Table 1). The reactionof the 3-O-mesyl xylofuranose derivative 4 gave the oxazoline 8 in 93% yield without formation of nucleophilic substitution products as with the tosylate 3. N-Pentofuranosyl oxazolines 9, 13 and 16 were synthesized in high 96-99% yields in acetonitrile (Table 1, entries 3,7 and 9) from isomeric benzoylated 1,2-O-isopropylidene-d-pentofuranose derivatives 5-6, and 15,prepared by the known methods decribed earlier from d-xylose and arabinose ^{17, 18, 19, 20, 21}. 1,2;3,5-Di-O-isopropylidene-d-xylofuranose (1) also afforded the protected xylofuranosyl oxazoline 12 in 76% yield as the result of regioselective transformations in the 1,2-O-isopropylidene group (Table 1, entry 6). The reactions of benzoyl-protected d-xylofuranose, ribofuranose and arabinofuranose 1,2-O-acetonides studied in acetonitrile at room temperature gave rise to the stereoselective formation of cis-fused bicyclic N-α- and β- d-pentofuranosyl oxazolines after the work-up of the reaction mixture without using column chromatography on silica gel (Table 1, entries 1-3, 6,7 and 9). Further, we explored scope of the BF₃^.Et₂O-KHF₂-mediatedreaction of benzoylated 1,2-O-isopropylidene-d-pentofuranose derivatives with other nitriles such as propionitrile and benzonitrile. The reaction 6 with benzonitrile or propionitrile gave oxazolines 10 and 11 in 97% and 86% yields, respectively (entries 4 and 5). The protected α-ribofuranosyl and β-arabinofuranosyl oxazolines 14 and 17 were smoothly prepared from the Ritter-like reactions of acylated 1,2-O-acetonides of 6 and 15 in benzonitrile in 97% yield (Table 1, entries 8 and 10). Next, the above stereoselective reactions were investigated for acyl-protected hexofuranose 1,2-O-acetonide derivatives under the similar conditions. 3,5,6-Tri-O-benzoyl-1,2-O-isopropylidene-α-d-glucofuranose (18) as well as isomeric allofuranose derivative 24, prepared according to the known methods ²², gave protected N-glycofuranosyl oxazolines 19 and 20 in acetonitrile and benzonitrile, oxazoline 25 in benzonitrile,respectively, in the high yields (Table 1, entries 11, 12 and 15). The Ritter reaction of fully O-acetylated 1,2-O-acetonide-α-d-glucofuranose 21²³ or α-d-allofuranose 26²⁴ in acetonitrile or benzonitrile furnished oxazolines 22 (entry 13), 23 (entry 14) and 27 (entry 16) in 95-98% yields. The structures of synthesized oxazolines were supported by ¹H, ¹³C NMR, IR spectral data and mass spectra (Experimental part).Resonance signals of CH₃ groups of oxazoline rings for all synthesized glycosyl oxazolines were observed as singlets in the range of ~ 1.97-2.18 ppm and 13.2-14.2 ppm ⁷ in ¹H and ¹³С NMR spectra, respectively, measured in CDCl₃. Signals of the tertiary carbon atoms of the sugar oxazolines with 2-Me, Et or Ph substituents displayed at 167-173 ppm in ¹³С NMR spectra. Absorption bands of

Synthesis of N-pentofuranosyl and N-hexofuranosyl oxazolines from protected d-sugar acetonides using BF3 OEt2-KHF2-promoted reactions with nitriles

Entry	Protected acetonide	Nitrile	Time (h)	KHF2/BF3.Et2O(Mol equiv)	Product	Yielda (%)
1	3	CH3CN	18	3.0/7.2	7	98%
2	4	CH3CN	18	3.1/7.2	8	93%
3	5	CH3CN	18	3.5/6.3	9	96%
4	5	C6H5CN	18	3.5/6.2	10	97%b
5	5	C2H5CN	18	2.7/4.9	11	86%c
6	1	CH3CN	4	2.1/6.2	12	76%
7	6	CH3CN	18	3.5/6.3	13	99%
8	6	C6H5CN	18	2.7/6.2	14	97%b
9	15	CH3CN	18	3.5/6.3	16	99%
10	15	C6H5CN	18	4.8/6.3	17	97%b
11	18	CH3CN	18	3.4/8.4	19	93%
12	18	C6H5CN	18	4.9/8.3	20	92%b
13	21	CH3CN	18	2.5/8.1	22	95%
14	21	C6H5CN	18	4.9/8.3	23	92%b
15	24	C6H5CN	18	4.3/8.3	25	86%b
16	26	CH3CN	18	2.4/8.0	27	98%

• a Isolated yield after basic treatment of reaction mixture without CC on silica gel

• b Isolated yield after column chromatography on silica gel

• c Yield was determined from 1H NMR spectral data of the reaction mixture

Thus, we have found that the Ritter-like reactions ^{25, 26} of the protected pentofuranose and hexofuranose 1,2-O-acetonides with nitriles in the presence of BF₃^.Et₂O and KHF₂ resulted in stereoselective transformations in the 1,3-dioxolane ring to give the only reaction products containing the five-membered 2-oxazoline derivatives. Next, to understand the assumed role of KHF₂ as a promoter with acidic properties in the studied conversions of acetonides 1, 3 and 5 into glycosyl α-D-oxazolines in the presence of BF₃^.Et₂O,the Ritter-like reaction of benzoylated d-xylofuranose 1,2-O-acetonide 5 was testedwith acetonitrile in the presence of 7.2 equiv of BF₃^.Et₂O and 3.4 equiv of p-toluenesulfonic acid instead of KHF₂ at room temperature (Scheme 3, conditions a).

The oxazoline 9 was prepared in 78% yield after column chromatography on silica gel.Besides, the BF₃^.Et₂O-KHF₂-assisted reaction of the tosylate 3 in acetonitrile was studied in the presence of NaBH₄ at room temperature (Scheme 3, conditions b). Such treatment of compound 3 did not result in the reduction of the C3-O-p-toluenesulfonyloxy group and acyclic product 30 was obtained in 40% yield after chromatography on silica gel. The structure of the xylitol derivative 30 was confirmed by the preparation of fully O-benzoylated derivative 31 (70%) and analysis of their ¹H and ¹³C NMR, HRMS spectral data. Proposed synthetic pathway to compound 30 via the possible reductive cleavage of the ketal-protected xylofuranose derivative 3 is outlined in Scheme 3. Activation of the 1,3-dioxolane ring in 3 may proceecd in the presence of the Lewis acid BF₃ or an acidic promoter with generation of intermediate 29 in the first step. Then, the formation of an intermediate oxocarbenium ion 29 occurs from 28. A selective reduction of aldofuranose counterpart of 29 with diborane forming in situ from NaBH₄ and BF₃ yields the selectively protected xylitol derivative 30 in the next steps (Scheme 3).The above findings indicate that the BF₃^.Et₂O-mediated reactions of benzoylated d-pentofuranose 1,2-acetonides imply a regioselective activation of the 1,2-O-isopropylidene group with involvement of the Lewis acid and acid promoters such as KF^.HF or p-TsOH, as with the Ritter-like reactions described for the fructofuranose acetonides in the presence of triflic acid ⁷or natural monosaccharides in liquid HF ²⁷.

Scheme 3.Study of BF3.OEt2-assisted transformations of protected xylofuranose acetonides 3 and 5 on the 1,3-dioxolane ring in acetonitrile. Reagents and conditions: (a) 5, CH3CN, p-TsOH, BF3.Et2O, rt, 18 h; 1N aq NaOH, 9, 78%; (b) 3, KHF2/BF3.Et2O, NaBH4, CH3CN, rt, 5% aq NaHCO3, 40%, 30; (c) BzCl, Py, rt, 31, 65%.

To further explore Ritter reactions, syntheses of the protected N-glycosyl oxazolines were investigated from the d-pentofuranose 1, 3, 5 and hexofuranose 18, 21, 24 acetonide derivatives under various Lewis acid-assisted conditions (Table 2).

The control Ritter reaction of xylofuranose acetonides 3 or 5 was tested in acetonitrile in the presence of catalytic amounts of BF₃^.Et₂O (0.5-0.8 equiv) and the excess of KHF₂ (3.5 equiv). No formation of oxazolines 7 and 9 was observed under these conditions (Table 2, entries 1 and 2). The reactions of acetonides 3 and 5 did not proceed in MeCN containing the excess of KHF₂ ora complex of KHF₂ with 18 crown 6 prepared previously in anhydrous methanol (entries 3 and 4). It was found that treatment of acetonides 3 and 5, unlike diacetonide 1 (entry 9), with 7.2 and 6.3 equiv of BF₃^.Et₂O in dry acetonitrile without KHF₂ led to oxazolines 7 and 9 in high 93% and 92% yields, respectively (entries 7 and 8).

Ritter reactions of benzoylated xylofuranosyl acetonide 5 with benzonitrile or propionitrile in the presence of6.0 or 4.9 of equiv BF₃^.Et₂O resulted in oxazolines 10 and 11 in 91% and 72% yields (entries 8 and 9). The Ritter reaction of O-benzoylated or acetylated 1,2-O-acetonide-d-glucofuranose derivatives 18 and 21 with benzonitrile in the presence of BF₃^.Et₂O (7.5 equiv) gave the oxazolines 20 and 23 in 44% and 40% yields (entries 12 and 13) compared to the same reactions under the BF₃^.Et₂O-KHF₂-promoted conditions (92% and 95%) (Table 1, entries 12 and 13). The allofuranosyl oxazoline derivative 25 was prepared in high yields using the BF₃^.Et₂O-KHF₂- or BF₃^.Et₂O conditions forRitter reactions of the D-allofuranose acetonide 24 with benzonitrile in the presence of 7.5 equiv of the Lewis acid (Table 2, entry 14 and Table 1, entry 15). Ritter reactions of the acetonide 3 with acetonitrile have been tested using the TMSOTf-KHF₂ or TMSOTf-mediated conditions (entries 15 and 16) and the oxazoline 7 was prepared in 98% and 95% yields, respectively.

After screening of various BF₃^.Et₂O-promoted reactions of xylofuranose acetonides 1, 3, and 5 with different protecting groups we have found that benzoyl-protected N-glycosyl oxazolines can be prepared in good yields under the BF₃^.Et₂O-KHF₂ (Table 1) or BF₃^.Et₂O (Table 2) conditions in the presence of the excess of the Lewis acid. In the case of a series of acylated hexofuranose 1,2-O-acetonide derivatives 18, 21, 24 and 26, the excess of the Lewis acid (about 8 equiv) along with KHF₂ (2.5-4.0 equiv), that may generate HF or HBF₄ and KBF₄ after interaction with the strong Lewis acid in polar solvent, needs for conversions of acetonides into oxazolines under the BF₃^.Et₂O-KHF₂ (Table 1, entries 11-16) with good yields compared to the BF₃^.Et₂O-promoted reactions for glucofuranose acetonides 18, 21 andallofuranose acetonide 24 (Table 2, entries 12-14). It is important to note that selection of optimal conditions (the use of the acidic promoter, ratio of reagents, excess of LW) for achieving high yields of glycosyl oxazolines in the Ritter reactions under consideration depends on the structure of the starting sugar, a character of protecting groups and nitrile used as solvent/reagent. Based on analysis of different conditions explored for a series of the Ritter-like reactions of sugar acetonides, mechanistic pathways leading to the formation of N-α-glycosyl oxazolines from protected xylofuranose acetonides 1, 3 and 5 were proposed (Scheme 4. and Scheme 5). Proposed mechanism for stereoselective BF₃^.Et₂O-KHF₂-assisted reactions of xylofuranose acetonide derivatives 3 and 5 with nitriles is illustrated in Scheme 4.

Scheme 4.Proposed mechanism for the formation of oxazolines from d-xylofuranose acetonide derivatives 3 and 5

The synthetic route to protected N-α-xylofuranosyl oxazolines likely to include the formation of intermediate ions 32a and 32b with assistance of a mild acidic promoter (gradual generation from KHF₂ in the presence of excess of BF₃^.Et₂O in polar solvent) and the Lewis acid, and the subsequent occurrence of oxocarbenium ions 33 and 34, respectively ^{12, 27}. We suggest that mechanistic pathway towards the nitrilium intermediate 35 from tosylate3may occur through a direct nitrile addition to the furanosyl oxocarbenium ion 33 from α or β-face and without remote participation of the protecting groups. The formation of the thermodynamically more stable the α-nitrilium ion 35 as compared with an intermediate β-nitrilium ion is probably favored by activated with the Lewis acid the 2-hydroxyl group, which is capable of stabilizing the adjacent cation via interaction with the α-nitrilium group in the presence of BF₃. Notice that the preferential generation of an intermediate stable α-nitrilium ion under the conversion of the protected xylofuranose derivative in CD₃CN in the presence of the Lewis acid (Me₃OBF₄) has been supported by Turnbull and co-workers using ¹H NMR experimental data and DFT calculations ²⁸.The kinetically controlled formation of the α-xylofuranosyl nitrilium ion 35 can result from the oxocarbenium ion 33 or contact tetrafluoroborate ion pairs via solvation of the intermediate oxonium cation under S_N1-reaction and a fast attack with nitrile from the α-face due to an anomeric effect, as has been reported for the glycosylation reactions of pyranose derivatives through pyranosyl nitrilium ions ^{29, 30, 31, 32}. The generation of oxazolinium intermediate 37²⁹ proceeds from the cation 36 via intramolecular trapping of the 2-O-hydroxyl group with the electrophilic nitrilium carbon.

Another possible pathway for formation of acylated N-α-xylofuranosyl oxazolines via generation of intermediate cyclic benzoxonium ions with participation of acyl protecting groups should be considered in the case of BF₃^.Et₂O-KHF₂-assisted reactions of benzoylated D-xylofuranose 1,2-O-acetonide5. α-Xylofuranosyl nitrilium intermediates may arise by nitrile addition to the intermediate cyclic 1,3(1,5)-dioxacarbenium ions, which would be produced via assistance of the O-benzoyl groups in the oxocarbenium ion 34 in the presence of the Lewis acid. The influence of vicinal and remote O-acyl groups has been invoked on many glycosylation reactions of monosaccharide derivatives in the presence of Lewis acids^{32, 33, 34}. The remote stereodirecting participation of 3-O- or 4-O-acyl (benzoyl, 4-methylbenzoyl or acetyl) protecting groups and their distinct stereochemical effects for promoted glycosylation reactions of protected pyranoses and furanosesas glycosyl donors have earlier been examined ^{34, 35}. An interesting concept of catalysis for the glycosylation reactions was reported which was introduced by the Schmidt group ^{36, 37, 38}. It includes activation of acceptor and glycosyl donor in the presence of Lewis acids as catalysts followed by generation of a cyclic intermediate to give rise to O-glycoside(s) as a result of the stereoselective glycosidation. From those mechanistic considerations, pathway for the BF₃^.Et₂O-KHF₂-promoted reaction ofacetonide5wasproposed (Scheme 4). One may pass through an intermediate transition state or complex 38 that originates from coordination of a transient glycosyl cation, stabilized by the remote participation of 3-O-benzoyl group in the oxocarbenium ion, with acetonitrile under assistance of the 2-OH group activated in the presence of BF₃^.Et₂O as a strong Lewis acid ^{32, 37}.

The further stereoselective course of the Ritter reaction ofacetonide 5would result inα-xylofuranosyl nitrilium ions39 and generation of an adduct 40 as a complex of the oxazoline with BF₃.The basic work-up of intermediate oxazolinium derivatives 37 and 40 with aqueous sodium hydroxide gave protected N-α-xylofuranosyl oxazolines 7, 9-11 (Scheme 4).

Two different pathways for BF₃^.Et₂O-promoted Ritter-like reactions of d-xylofuranose diacetonide 1, bearing non-participating isopropylidene groups, are shown in Scheme 5.

Scheme 5.Proposed intermediates during BF3.Et2O-promoted reactions of diacetonide 1 with acetonitrile

The formation of the oxazoline 12 from diacetonide 1 in acetonitrile under the BF₃^.Et₂O-KHF₂-assistedconditions (a) may proceed via the oxocarbenium ion 41 after a regioselective activation of the 1,2-O-isopropylidene group with an acidic promoterand the Lewis acid followed by generation of the oxazolinium intermediate 42 similar to conversions of the 3-O-tosyl xylofuranose derivative 3 (Scheme 4) into the oxazoline 7 throughthe cation 36 and key oxazolinium derivative 37. Under the BF₃^.Et₂O-mediatedconditions (b), the Ritter-like reaction of 1 with acetonitrile would occur in a different pathway through activation of the 1,3-dioxolane ring with BF₃^.Et₂O in the first step, generation of the oxocarbenium ion 43 and a subsequent bottom attack of solvent to give the β-nitrilium intermediate 44, as has been reported for the preparation of oxazolines by reacting epoxides with nitriles in the presence of Lewis acids ^{11, 39}. The further inversion of 44 at C1 with acetonitrile would result in an intermediate α-nitrilium ion, and subsequently the electrophilic α-nitrilium cation 45, a complex of the oxazoline with the Lewis acid 46, giving the target oxazoline 16 after the basic work-up.

In order to explore the scope of the BF₃^.Et₂O-mediated approachfor other protected d-pentofuranose derivatives with free hydroxyl groups we have undertaken synthesis of N-xylofuranosyl oxazolines from selectively benzoylated xylofuranoses 47-48 readily prepared by the acidic removal of 1,2-O-isopropylidene groups from xylofuranose acetonide derivatives 2 and 5 with aqueous trifluoroacetic acid (Scheme 6, conditions a_1-2). 5-O-Benzoyl-α,β-d-xylofuranose (47) gave the benzoyl-protected oxazoline 49 (75%) under the the KHF₂-BF₃^.Et₂O conditions (conditions b₁). Interestingly, the reaction of 3,5-di-O-benzoyl-α,β-d-xylofuranose (48) in acetonitrile furnished the oxazoline 9 (99%), as in the case of the Ritter reaction of 3,5-di-O-benzoyl-1,2-O-isopropylidene-α-d-xylofuranose (5) (Table 1, entry 3).

In addition, the Ritter-like reaction of 48 with acetonitrile in the presence of BF₃^.Et₂O (6.0 equiv) without KHF₂ (conditions c₁) also afforded the protected N-α-xylofuranosyl oxazoline 9 (65%). Furthermore, we have found that the Lewis acid promoted reactions of 1,3,5-tri-O-benzoyl-α-d-ribofuranose (50)⁴⁰ with CH₃CN in the presence of KHF₂ or without the inorganic salt gave the α-oxazoline 13 in 99% and 65% yields, respectively, after the basic work-up of reaction mixtures (Scheme 6, conditions b₂ and c₂). Removing benzoyl protecting groups in the oxazoline 17 with NH₃/MeOH (conditions d) resulted in the β-arabinofuranosyl oxazoline 51 (93%). Acetylation of the latter with acetic anhydride in pyridine at room temperature afforded fully O-acetylated oxazoline 52 in 80% yield.

Scheme 6.Synthesis of acylated d-xylo-, ribo- and arabinofuranosyl oxazolines. Reagents and conditions: (a1) 2, 93% aq TFA, rt, 2 h, 47, 80%; (a2) 5, 93% aq TFA, rt, 2 h, 48, 80%; (b1) benzoylated d-xylofuranoses 47-48, CH3CN, KHF2,BF3.Et2O, rt; 3-4 h, 5 % aq NaHCO3, 49, 75%; 9, 99%; (c1) 48, CH3CN/ BF3.Et2O, rt, 3 h, 5 % aq NaHCO3,9, 65%; (b2) 50, CH3CN, KHF2, BF3.Et2O, rt; 3 h, 1N aq NaOH,13, 99%; (c2) 50, CH3CN, BF3.Et2O, rt, 3 h, 1N aq NaOH,13, 65%; d) 17, NH3/MeOH, rt, 18 h, 51, 93%; e) 51, Ac2O, Py, rt, 52, 80%.

From the above-considered synthetic routes to oxazolines from protected d-pentofuranose derivatives it should be noted that the BF₃^.Et₂O-promoted reactions of selectively acylated d-xylofuranose and -ribofuranose derivatives (Scheme 6), diacetonide 1 (Scheme 5) and acylated 1,2-O-isopropylidene-α-d-pentofuranoses 3, 5, 6 and 15 (Scheme 4 and Scheme 3) differ in producing intermediate oxocarbenium ions in the presence of the Lewis acid in the first steps and, probably, different oxazolinium intermediates in the next steps. The formation of α-nitrilium ions is the general peculiarity for the Ritter-like transformations of d-xylofuranose and -ribofuranose derivatives studied with nitriles. Prepared sugar oxazolines can be used for obtaining various N-glycosyl amides via hydrolysis reactions and novel N-glycoside derivatives.

A series of newly synthesized N-glycosyl oxazoline derivatives with 2-phenyl substituent were tested for their in vitro inhibitory effects on proliferation of myelogenous leukemia (K562), cervical carcinoma (Hela) and breast carcinoma (MCF-7) using the resazurin assay ⁴¹ that, together with other high-throughput screening methods, had been developed previously to measure viability or cytotoxicity ⁴². 5-Fluorouracil (5-FU) was used as the reference compound. The findings are listed in Table 3.

Among N-pentofuranosyl oxazolines with xylo-, ribo- and arabino-configurations tested(compounds 10, 14, 17, 51 and 52), only benzoylated xylo- and arabinofuranosyl oxazolines 10 and 17 displayed weak inhibitory effects against MCF cell line with IC₅₀ values of 99.76 and 79.4 ϻM, respectively. Unlike to isomeric xylo- and arabino-furanosyl oxazolines 10 and 17, 3,5-di-O-benzoyl α-ribofuranosyl oxazoline 14 showed moderate activity with IC₅₀ value of 63.92 ϻM in Hela cells and good antiproliferative activity against K562 cell line (IC₅₀ 23.01 ϻM). Deprotected N-β-d-arabinofuranosyl oxazoline 51 did not show activity on all cell lines at the highest concentration of tested compound. The benzoylated N-α-glycofuranosyl oxazoline derivative 20,bearing 2-phenyl substituent in the oxazoline ring,displayed significant antiproliferative activity with IC₅₀ value (21.92 ϻM) comparable to those of the knownnucleobase analog 5-FU on Hela cells. Comparative biological assessment of the oxazoline 20 and itsclose structural analogs the N-glycosyl oxazoline derivatives 23 and 25 is underway in cancer cell lines. To gain insight into the mode action/mechanism for the inhibitory effects of the oxazolines with 2-phenyl substituent, the apoptosis assays for compound 20 as well as its two analogs are currently under investigation in Hela cancer cell line, applying DAPI and Annexin V-FITC/PI staining methods, and the results will be published elsewhere.

a₁. Synthesis 2-alkyl-α-D-pentofurano-(1,2-d)-2-oxazoline derivatives under the BF₃^.Et₂O-KHF₂-promoted conditions. To a stirred solution of pentofuranose acetonide derivative (1.4 mmol) in anhydrous acetonitrile (8.6 ml) or benzonitrile (3.8 ml) KHF₂ (4.8 mmol) and boron trifluoride diethyl etherate (1.42 ml,10.3 mmol) were added successively. The resulting solution was stirred at room temperature for 18 h, and then the reaction mixture was poured into cooled 22.6 ml 1N aq NaOH. The aqueous phase was extracted with CHCl₃ (3x100 ml). The combined organic extracts were washed with water, dried over anh. Na₂SO₄, and evaporated to dryness. Oxazolines 7-8, 11-13 were prepared in 76-99% yields, and oxazolines 10, 14, 17with 2-phenyl substituentwere isolated in 97% yield after column chromatography on silica gel using for elution mixtures of hexane-ethylacetate and ethylacetate-methanol 6:1.

a₂. Synthesis 2-methyl-α-D-pentofurano-(1,2-d)-2-oxazoline derivatives under the BF₃^.Et₂O-promoted conditions. To a stirred solution of xylofuranose acetonide derivative (0.2 mmol) in anhydrous acetonitrile (1.5 ml) boron trifluoride diethyl etherate (0.2 ml, 1.44 mmol) was added successively. The resulting solution was stirred at room temperature for 18 h, and then the reaction mixture was poured into cooled 5% aq. NaHCO₃. The aqueous phase was extracted with CHCl₃ (3x50 ml). The combined organic extracts were washed with water, dried over anh. Na₂SO₄, and evaporated to dryness. Oxazolines 7, 9 and 12 were prepared in 54-93% yields.

a₁. To a stirred solution of acylated glucofuranose or allofuranose acetonide (0.4 mmol) in anhydrous benzonitrile (3.8 ml) or acetonitrile (3.1 ml) KHF₂ (1.95 mmol) and boron trifluoride diethyl etherate (0.45 ml, 3.3 mmol) were added successively. The reaction mixture was stirred at room temperature for 18 h, and then poured into cooled 7.3 ml 1N aq NaOH. The aqueous phase was extracted with CHCl₃ (3x30 ml). The combined organic extracts were washed with water, dried over anh. Na₂SO₄, and evaporated. Oxazolines with 2-phenyl substituent were isolated by column chromatography on silica gel using for elution mixtures of hexane-ethylacetate 6:1, 4:1, 2:1, and ethylacetate or ethylacetate-methanol 6:1. Oxazolines 19-20, 22-23 and 25, 27 were prepared in 86-98% yields.

Yield (98%), a colorless oil(methoda₁).(α)_D²⁰–44.4 (c 0.5, CHCl₃). IR (film, CCl₄): ν 1725, 1670, 1615, 1375, 1272 cm^-1. ¹Н NMR (500 MHz, CDCl₃) δ = 7.38-7.85 (m, 9H, СОC₆H₅ and ОSO₂C₆H₄CH₃), 6.09 (d, 1Н, J_1,2 = 5.4 Hz, Н-1), 5.02 (d, 1Н, J_3,4 = 3.0 Hz, Н-3), 4.86 (d, 1Н,Н-2), 4.33 (dd, 1Н, J_5,4 = 6.2, J_5,5′ = 11.3 Hz, Н-5), 4.22 (dd, 1Н, J_5′,4 = 5.7 Hz, Н-5′), 3.98-4.01 (m, 1Н, Н-4), 2.31 (s, 3H, ОSO₂C₆H₄CH₃), 1.96 (s, 3H, NCH₃). ¹³C NMR (126 MHz, CDCl₃) δ = 167.4 (CN), 164.9 (C=O, СОC₆H₅), 145.6, 133.4, 130.3, 129.2, 128.5, 127.6 (СОC₆H₅ andОSO₂C₆H₄CH₃), 100.2 (С-1), 88.4 (C-4), 81.1, 74.2 (C-2, С-3), 60.3 (С-5), 21.0 (ОSO₂C₆H₄CH₃), 13.2 (NMe).HRMS (ESI⁺):m/z calcd for C₂₁H₂₁NO₇S (M+H)⁺: 432.1117, found 432.1120; and C₂₁H₂₁NO₇SNa (M+Na)⁺: 454.0936, found 454.0935.

Yield (93%), a colorless oil (methoda₁).(α)_D²⁰–35.1 (c 0.8, CHCl₃). IR (film): ν 1722, 1675, 1357, 1275 cm^-1. ¹Н NMR (500 MHz, CDCl₃) δ =7.47-8.09 (m, 5H, СОC₆H₅), 6.22 (d, 1Н, J_1,2=5.6 Hz, Н-1), 5.23 (d, 1Н, J_3,4 = 3.1 Hz, Н-3), 5.09 (d, 1Н,Н-2), 4.66 (dd, 1Н, J_5,4 = 6.3, J_5,5′ = 11.8 Hz, Н-5), 4.62 (dd, 1Н, J_5′,4 = 3.4 Hz, Н-5′), 4.13-4.16 (m, 1Н, Н-4), 3.16 (s, 3H, ОSO₂CH₃), 2.12 (s, 3H, NCH₃). ¹³C NMR (126 MHz, CDCl₃) δ = 168.8 (CN), 166.1 (C=O, СОC₆H₅), 133.5, 129.8, 129.3, 128.5, (СОC₆H₅), 100.8 (С-1), 84.2 (C-4), 77.3, 75.1 (C-2, С-3), 60.8 (С-5), 38.5 (ОSO₂CH₃), 13.9 (NMe). HRMS (ESI⁺): m/z calcd for C₁₅H₁₇NO₇S (M+H)⁺:356.0798, found 356.0791; and C₂₁H₂₁NO₇SNa (M+Na)⁺: 378.0610, found 378.0511.

Yield (96%), foam (method a₁). (α)_D²⁰–73.2 (c 1.0, CHCl₃). IR (KBr): ν 1722, 1672, 1364, 1275, 1180 cm^-1.¹Н NMR (500 MHz, CDCl₃) δ = 7.39-8.04 (m, 10H, 2 x СОC₆H₅), 6.21 (d, 1Н, J_1,2 =5.7 Hz, Н-1), 5.59 (d, 1Н, J_3,4 = 3.2 Hz, Н-3), 4.86 (d, 1Н, J_2,1 = 5.7 Hz, Н-2), 4.64 (d, 2Н, H-5, Н-5´), 4.19-4.25 (m, 1Н, Н-4), 2.1 (s, 3H, NCH₃). ¹³C NMR (126 MHz, CDCl₃) δ = 166.7 (CN), 166.1 and 165.2 (C=O, 2хСОC₆H₅), 140.2, 140.0, 131.3, 131.2, 128.9, 128.8, 128.7, 128.2 (2хСОC₆H₅), 100.8 (С-1), 84.6 (C-4), 76.3, 75.5 (C-2, С-3), 61.6 (С-5), 13.8 (NMe). HRMS (ESI⁺):m/z calcd for C₂₁H₁₉NO₆ (M+H)⁺: 382.1285, found 382.1287.

Yield(97%), a colorless oil (method a₁). (α)_D²⁰-27.5 (c 1.0, CHCl₃). IR (KBr): ν 1725, 1665, 1268, 1112 cm^-1.¹Н NMR (500 MHz, CDCl₃) δ = 7.42-8.13 (m, 15H, 2 x СОC₆H₅, -N=C-C₆H₅), 6.52 (d, 1Н, J_1,2 =4.0 Hz, Н-1), 5.79 (d, 1Н, J_3,4 = 3.0 Hz, Н-3), 5.15 (d, 1Н, J_2,1 = 4.0 Hz, Н-2), 4.74 (d, 2Н, H-5, Н-5´), 4.33-4.36 (m, 1Н, Н-4). ¹³C NMR (126 MHz, CDCl₃) δ = 167.0 (CN), 166.1 and 165.4 (C=O, 2хСОC₆H₅), 133.9, 133.2, 132.8, 129.9, 129.8, 129.2, 128.7, 128.6, 128.4 (2хСОC₆H₅, -N=C-C₆H₅), 100.8 (С-1), 84.8 (C-4), 76.4, 75.6 (C-2, С-3), 61.5 (С-5). HRMS (ESI⁺):m/z calcd for C₂₆H₂₁NO₆ (M+Na)⁺: 466.1261, found 466.1263.

Yield (86%), foam,(method a₁). (α)_D²⁰- 36.3 (c 1.0, CHCl₃). IR (KBr): ν 1724, 1670, 1363, 1275, 1182 cm^-1. ¹Н NMR (500 MHz, CDCl₃) δ = 7.44-8.09 (m, 10H, 2 x СОC₆H₅), 6.29 (d, 1Н, J_1,2 = 5.7 Hz, Н-1), 5.65 (d, 1Н, J_3,4 = 3.2 Hz, Н-3), 4.92 (d, 1Н, J_2,1 = 5.7 Hz, Н-2), 4.70 (d, 2Н, H-5, Н-5´), 4.21-4.28 (m, 1Н, Н-4), 2.45-2.49 (m, 2Н, -N=C-СН₂СН₃), 1.29 (t, 3H, -N=C-СН₂СН₃). ¹³C NMR (126 MHz, CDCl₃) δ = 173.1 (CN), 166.2 and 165.3 (C=O, 2хСОC₆H₅), 133.8, 133.3, 129.9, 129.8, 129.5, 128.9, 128.7, 128.4 (2хСОC₆H₅), 100.6 (С-1), 84.5 (C-4), 76.3, 75.4 (C-2, С-3), 61.6 (С-5), 21.5 (N=C-СН₂СН₃), 10.2 (N=C-СН₂СН₃). HRMS (ESI⁺): m/z calcd for C₂₁H₂₁NO₆ (M+H)⁺: 396.1442, found 396.1446.

Yield (76%), oil (methoda₁).(α)_D²⁰+6.9 (c 1.0, CHCl₃). IR (film): ν 2993, 2940, 1669, 1384, 1228, 1043 cm^-1. ¹Н NMR (500 MHz, CDCl₃) δ = 6.10 (d, 1Н, J_1,2 = 5.5 Hz, Н-1), 4.65 (d, 1Н, J_2,1 = 5,5 Hz, Н-2), 4.30 (d, 1Н, J_3,4 = 2.4 Hz,Н-3), 4.09 (dd, 1Н, J_5,4 = 2.5, J_5,5′ = 13.6 Hz, Н-5), 4,07 (d, 1Н, Н-5′), 3.47-3.3.49 (m, 1Н, Н-4), 2.00 (s, 3H, NCH₃), 1.42 and 1.36 (2 s, 3H, (CH₃)₂C-)). ¹³C NMR (126 MHz, CDCl₃) δ: 168.3 (CN), 101.3 (С-1), 97.7 ( C-CH₃)₂), 85.9 (C-4), 72.9, 69.6 (C-2, С-3), 59.5 (С-5), 28.8 and 18.6 ((CH₃)₂C-), 13.7 (NMe). HRMS (ESI⁺): m/z calcd for C₁₀H₁₅NO₄ (M+H)⁺: 214.1074, found 214.1084.

Yield (99%), a colorless oil (method a₁). (α)_D²⁰+74.5 (c 1.0, CHCl₃). IR (film): ν 1729, 1665, 1272, 1119 cm^-1. ¹Н NMR (500 MHz, CDCl₃) δ = 7.40-8.08 (m, 10H, 2 x СОC₆H₅), 6.17 (d, 1Н, J_1,2 =5.5 Hz, Н-1), 5.22 (t, 1Н, J_2,1 =5.5, J_2,3 =5.7 Hz, Н-2), 5.16 (dd, 1Н, J_3,4 = 9.0 Hz, Н-3), 4.75 (dd, 1Н, J_5,4 =3.6, J_5,5′ =12.0 Hz, Н-5), 4.57 (dd, 1Н, J_5′,4 =5.2 Hz, Н-5′), 4.19-4.23 (m, 1Н, Н-4), 2.1 (s, 3H, NCH₃). ¹³C NMR (CDCl₃) δ = 169.7 (CN), 166.1 and 165.5 (C=O, 2хСОC₆H₅), 133.6, 133.2, 129.8, 129.7, 129.4, 128.8, 128.5, 128.3 (2хСОC₆H₅), 100.6 (С-1), 78.5 (C-4), 74.1, 74.0 (C-2, С-3), 63.0 (С-5), 13.8 (NMe). HRMS (ESI⁺):m/z calcd for C₂₁H₁₉NO₆ (M+H)⁺: 382.1285, found 382.1287.

Yield (97%), a white solid (method a₁). M.p. 128-129 ^oC. (α)_D²⁰+113.8 (c 1.0, CHCl₃). IR (KBr): ν 1739, 1716, 1646, 1277, 1101 cm^-1.¹Н NMR (500 MHz, CDCl₃) δ = 7.35-8.04 (m, 15H, 2 x СОC₆H₅, -N=C-C₆H₅), 6.37 (d, 1Н, J_1,2 =5.6 Hz, Н-1), 5.38 (t, 1Н, J_3,2 = 5.7 Hz, Н-2), 5.24 (d, 1Н, J_3,4 =J_3,2 = 5.9 Hz, Н-3), 4.72 (dd, 1Н, J_5,4 = 4.7, J_5,5́ = 12.1 Hz, H-5), 4.55 (dd, 1Н, J₅´_,4 = 4.7 Hz, Н-5´), 4.20-4.24 (m, 1Н, Н-4). ¹³C NMR (126 MHz, CDCl₃) δ = 167.5 (CN), 166.1 and 165.7 (C=O, 2хСОC₆H₅), 133.6, 133.1, 132.5, 129.8, 129.7, 129.4, 128.9, 128.8, 128.5 (2хСОC₆H₅, -N=C-C₆H₅), 100.8 (С-1), 78.4 (C-4), 74.1, 74.09 (C-2, С-3), 63.0 (С-5). HRMS (ESI⁺):m/z calcd for C₂₆H₂₁NO₆ (M+Na)⁺: 466.1261, found 466.1264.

Yield (99%), a colorless oil (methoda₁).(α)_D²⁰-36.1 (c 1.0, CHCl₃). IR (KBr): ν 1725, 1669, 1321, 1269, 1108 см^-1.¹Н NMR (500 MHz, CDCl₃) δ = 7.41-8.06 (m, 10H, 2 x СОC₆H₅), 6.14 (d, 1Н, J_1,2 = 5.4 Hz, Н-1), 5.51 (br.d, 1Н, J_3,4 = 2.5, J_3,2 = 1.2 Hz, Н-3), 4.98 (br. d, 1Н, J_2,1 = 5.5 Hz, Н-2), 4,54-4,57 (m, 1Н, Н-4), 4,39 (dd, 1Н, J_5,4 = 6.2, J_5,5′ =11.7 Hz, Н-5), 4.36 (dd, 1Н, J_5′,4=3.9 Hz, Н-5′), 2.07 (s, 3H, NCH₃). ¹³C NMR (126 MHz, CDCl₃) δ = 168.7 (CN), 166.1 and 165.4 (C=O, 2хСОC₆H₅), 133.7, 133.1, 129.8, 129.8, 129.6, 128.8, 128.5, 128.3 (2хСОC₆H₅), 101.8 (С-1), 86.4 (C-4), 80.7, 79.0 (C-2, С-3), 63.7 (С-5), 14.3 (NMe). HRMS (ESI⁺):m/z calcd for C₂₁H₁₉NO₆ (M+H)⁺: 382.1285, found 382.1287.

Yield (97%), a colorless oil (methoda₁).(α)_D²⁰-8.5 (c 1.0, CHCl₃). IR (film): ν 1721, 1642, 1269, 1109 cm^-1. ¹Н NMR (500 MHz, CDCl₃) δ = 7.30-8.14 (m, 15H, 2 x СОC₆H₅, -N=C-C₆H₅), 6.46 (d, 1Н, J_1,2 =5.7 Hz, Н-1), 5.76 (d, 1Н, J_3,4 = 2.6 Hz, Н-3), 5.29 (d, 1Н, J_2,1 = 5.7 Hz, Н-2), 4.65-4.68 (m, 1Н, Н-4), 4.48 (dd, 1Н, J_5,4 5.8, J_5,5′ = 11.6 Hz, Н-5), 4.38 (dd, 1Н, J_5′,4 = 6.4 Hz, Н-5′). ¹³C NMR (126 MHz, CDCl₃) δ = 166.9 (CN), 166.1 and 165.5 (C=O, 2хСОC₆H₅), 133.8, 133.1, 132.8, 129.9, 129.8, 129.2, 128.7, 128.6, 128.3 (2хСОC₆H₅, -N=C-C₆H₅), 100.9 (С-1), 86.7 (C-4), 81.4, 79.3 (C-2, С-3), 63.8 (С-5). HRMS (ESI⁺): m/z calcd for C₂₆H₂₁NO₆ (M+Na)⁺: 466.1261, found 466.1265.

Yield (93%), a colorless oil (methoda₁).(α)_D²⁰-173.0 (c 1.0, CHCl₃). IR (film): ν 1725, 1667, 1375, 1266 cm^-1. ¹Н NMR (500 MHz, CDCl₃) δ = 7.40-8.04 (m, 15H, 3 x СОC₆H₅), 6.26 (d, 1Н, J_1,2 = 5.6 Hz, Н-1), 5.90-5.93 (m, 1H, Н-5), 5.62 (dd, 1Н, J_3,4 = 3.1 Hz, Н-3), 5.02 (dd, 1Н, Н-6), 4.90 (d, 1Н,Н-2), 4.63 (dd, 1Н, Н-6′), 4.27 (dd, 1Н, Н-4), 2.18 (s, 3H, NCH₃). ¹³C NMR (125 MHz, CDCl₃) δ = 169.04 (CN), 166.11, 165.3 and 165.1 (C=O, 3хСОC₆H₅), 133.69, 133.27, 133.06, 131.18, 129.9, 129.73, 129.68, 128.56 128.37 (3хСОC₆H₅), 100.88 (С-1), 84.56, 75.71, 75.64, 75.51 (C-4, C-5, C-2, С-3), 64.25 (С-6), 13.9 (NMe). HRMS (ESI⁺):m/z calcd for C₂₉H₂₅NO₈ (M+Na)⁺: 538.1478, found 538.1453.

Yield (92%), a colorless oil (methoda₁).(α)_D²⁰-34.6 (c 1.0, CHCl₃). IR (KBr): ν 1728, 1646, 1268, 1102 cm^-1.¹Н NMR (500 MHz, CDCl₃) δ = 7.36-8.15 (m, 20H, 2 x СОC₆H₅, -N=C-C₆H₅), 6.52 (d, 1Н, J_1,2 = 5.5 Hz, Н-1), 5.95-5.99 (m, 1Н, Н-5), 5.75 (d, 1Н, J_3,4 = 3.0 Hz, Н-3), 5.13 (d, 1Н, J_2,1 = 5.5 Hz, Н-2), 5.06 (dd, 1Н, J_6,5 = 5.8, J_6,6′ = 11.6 Hz, H-6), 4.65 (dd, 1Н, J_6,5 = 5.4 Hz, H-6´), 4.36 (dd, 1Н, Н-4). ¹³C NMR (126 MHz, CDCl₃) δ = 166.9 (CN), 166.0, 165.3 and 165.0 (C=O, 3хСОC₆H₅), 133.6, 133.1, 132.9, 132.7, 129.8, 129.6, 128.6, 128.5, 128.2 (3хСОC₆H₅, -N=C-C₆H₅), 100.9 (С-1), 84.8, 75.6, 75.6, 68.4 (C-5, C-4, C-2, С-3), 64.2 (С-6). HRMS (ESI⁺):m/z calcd for C₃₄H₂₇NO₈ (M+Na)⁺: 600.1634, found 600.1630.

Yield (95%), a colorless oil (methoda₁).(α)_D²⁰+7.2 (c 1.0, CHCl₃). IR (film): ν 1743, 1662, 1375, 1243 cm^-1. ¹Н NMR (500 MHz, CDCl₃) δ = 6.07 (d, 1Н, J_1,2=5.6 Hz, Н-1), 5.34 (br.s, 1H, H-3), 5.23-5.26 (m, 1H, Н-5), 4.63 (d, 1Н, J_3,4 = 3.1 Hz, Н-2), 4.54(dm, 1H, H-4), 4.04 (dd, 1Н, Н-6), 3.82 (dd, 1Н,Н-6’), 2.06, 2.05, 2.02, and 1.97 (4s, 3H, 3x COCH₃, NCH₃).¹³C NMR (126 MHz, CDCl₃) δ= 170.6 (CN), 169.6, 169.6 and 168.8 (C=O, 3хСОCH₃), 100.9 (С-1), 84.5, 75.2, 74.3, 67.5 (C-4, C-5, C-2, С-3), 63.4 (С-6), 20.8 and 20.7 (3хСОCH₃), 13.9 (NMe). HRMS (ESI⁺): m/z calcd for C₁₄H₁₉NO₈ (M+Na)⁺: 352.1003, found 352.1006.

Yield (92%), a white solid (method a₁).M.p. 169-172 ⁰С.(α)_D²⁰+25.0 (c 1.0, CHCl₃).¹Н NMR (500 MHz, CDCl₃) δ = 7.43-8.02 (m, 5H, Ph), 6.33 (d, 1Н, J_1,2=5.5 Hz, Н-1), 5.49 (d, 1H, J_3,2 = 3.0 Hz, H-3), 5.31 (ddd, 1H, Н-5), 4.86 (d, 1Н, J_2,1 = 5.5 Hz, Н-2), 4.60 (dd, 1Н, J_6,5 = 2.1, J_6,6′ = 12.3 Hz, Н-6), 4.08 (dd, 1Н, J_6,5 = 5.8, Н-6'), 3.91 (dd, 1H, H-4), 2.11, 2.01 and 1.99 (3s, 3H, 3xCOCH₃).¹³C NMR (126 MHz, CDCl₃) δ: 170.7 (-C=N), 169.75, 169.71 and 166.6 (C=O, 3хСОCH₃), 113.3, 129.1, 128.6, 115.9 (Ph-C=N-), 101.1 (С-1), 84.5, 75.4, 74.5, 67.5 (C-4, C-5, C-2, С-3), 63.4 (С-6), 20.81 and 20.76 (3хСОCH₃). HRMS (ESI⁺): m/z calcd for C₁₈H₂₁NO₈ (M+Na)⁺: 402.1003, found 402.1008.

Yield (86%), a colorless oil (method a₁).(α)_D²⁰+58.5 (c 1.0, CHCl₃). IR (film): ν 1728, 1649, 1265, 1118 cm^-1.¹Н NMR (500 MHz, CDCl₃) δ = 7.29-8.00 (m, 15H, 3 x СОC₆H₅), 6.40 (d, 1Н, J_1,2 = 5.6 Hz, Н-1), 5.87-5.90 (m, 1H, Н-5), 5.43-5.47 (m, 2Н,H-2 and Н-3), 4.88 (dd, 1Н, J_6,5 = 3.3, J_6,6′ = 12.1 Hz, Н-6), 4.68 (dd, 1Н, J_6,5 = 6.8 Hz, Н-6′), 4.27 (dd, 1Н, Н-4). ¹³C NMR (125 MHz, CDCl₃) δ = 166.8 (-C=N), 166.1, 165.54 and 165.5 (C=O, 3хСОC₆H_5, C₆H₅), 133.4, 133.2, 133.1, 132.6, 129.8, 129.7, 129.0, 128.5, 128.4, 128.3,128.2 (3хСОC₆H_5, Ph-C=N-), 100.8 (С-1), 78.6, 75.1, 74.7, 71.2 (C-4, C-5, C-2, С-3), 63.4 (С-6). HRMS (ESI⁺):m/z calcd for C₃₄H₂₇NO₈ (M+H)⁺: 578.1810, found 578.1816; (M+Na)⁺: 600.1634, found 600.1637.

Yield (98%), a colorless oil (methoda₁).(α)_D²⁰+107.2 (c 1.0, CHCl₃). IR (film): ν 17440, 1667, 1375, 1247 cm^-1. ¹Н NMR (500 MHz, CDCl₃) δ = 6.01 (d, 1Н, J_1,2=5.6 Hz, Н-1), 5.34 (dm, 1H, H-5), 5.02 (t, 1Н, J_2,3 = 5.8 Hz, Н-2), 4.94 (dd, 1H, H-3), 4.41(dd, 1H, H-4), 4.14 (dd, 1Н, Н-6), 3.80 (dd, 1Н,Н-6’), 2.16, 2.11, 2.10, and 2.08 (4s, 3H, 3x COCH₃, NCH₃). ¹³C NMR (126 MHz, CDCl₃) δ = 170.5 (CN), 169.8, 169.7 and 169.6 (C=O, 3хСОCH₃), 100.4 (С-1), 78.2, 74.5, 73.9, 70.0 (C-4, C-5, C-2, С-3), 62.3 (С-6), 20.8, 20.7 and 20.4(3хСОCH₃), 13.9 (NMe). HRMS (ESI⁺): m/z calcd for C₁₄H₁₉NO₈ (M+Na)⁺: 352.1003, found 352.1004.

To a stirred solution of acetonide 3 (147 mg, 0.33 mmol) in anhydrous acetonitrile (1.9 ml) KHF₂ (103 mg, 1.32 mmol), NaBH₄ (59 mg, 1.5 mmol) and then boron trifluoride diethyl etherate (1.42 ml, 11.38 mmol) were added successively. The reaction mixture was stirred at room temperature for 18 h, and then was gradually poured into cooled 5% NaHCO₃.The aqueous phase was extracted with CHCl₃ (3x30 ml). The combined organic extracts were washed water, dried over anh. Na₂SO₄, and evaporated to dryness. The residue was chromatographed on silica gel, using for elution a mixture of hexane-ethylacetate 6:1 and 3:1, and 1:2 as the eluent to give the starting acetonide 3 (38 mg, 26%) and the xylitol derivative 30 (59 mg, 40%) as a colorless oil. (α)_D²⁰+1.4 (c 0.5, CHCl₃). ¹Н NMR (500 MHz, CDCl₃) δ = 7.30-8.03 (m, 9H, СОC₆H₅ and ОSO₂C₆H₄CH₃), 4.84 (dd, 1Н), 4.31-4.38 (m, 2Н), 3.90-3.97 (m, 3Н), 3.82-3.91 (m, 2Н), 2.41 (s, 3H, ОSO₂C₆H₄CH₃), 1.22 (d, 3H, (CH₃)CH-), 1.21 (d, 3H, (CH₃)CH-). ¹³C NMR (126 MHz, CDCl₃) δ = 165.9 (C=O, СОC₆H₅), 145.4, 133.3, 130.0, 129.8, 129.7, 128.5 (СОC₆H₅ andОSO₂C₆H₄CH₃), 78.3, 75.5, 72.2, 65.5, 64.5 (-CH₂OBz), 59.9 (-CH₂OH), 22.8 ((CH₃)₂CH-), 22.7 ((CH₃)₂CH-), 21.7 (ОSO₂C₆H₄CH₃). HRMS (ESI⁺): m/z calcd for C₂₂H₂₂O₈SNa (M+Na)⁺: 475.1403, found 475.1391.

To a stirred solution of xylitol derivative 30 (45 mg, 0.099 mmol) in anhydrous pyridine (2 ml) BzCl (0.068 ml, 0.57 mmol) was added at 0 ^oС and then the reaction mixture was stirred for 48 h at room temperature, diluted with CH₂Cl₂ and poured into cold 5% aq NaHCO₃. The aqueous phase was extracted with CH₂Cl₂ (3x50 ml), the combined organic extracts were washed with water, dried and evaporated. The residue was chromatographed on a silica gel, using for elution a mixture of hexane-ethylacetate 6:1, 5:1, and chloroform to give (42.7 mg,65%) of protected xylitol derivative 31 as a colorless oil. (α)_D²⁰-17.8 (c 0.79, CHCl₃).¹Н NMR (500 MHz, CDCl₃) δ = 7.40-8.18 (m, 15H, 3xСОC₆H₅), 7.77 and 7.11 (2d, 4H, ОSO₂C₆H₄CH₃), 5.91 (q, 1Н, H-4), 5.26 (dd, 1H, H-3 ), 4.64 (dd,1H, H-5), 4.60 (dd,1H, H-5′), 4.54 (dd, 1H, H-1), 4.47 (dd, 1H, H-1′), 4.19-4.22 (m, 1Н, H-2), 3.89-3.94 (m, 1Н, (CH₃)₂CH-), 2.30 (s, 3H, ОSO₂C₆H₄CH₃), 1.25 (d, 3H, (CH₃)CH-), 1.21 (d, 3H, (CH₃)CH-). ¹³C NMR (126 MHz, CDCl₃) δ = 166.1, 165.8, and 165.3 (C=O, 3xСОC₆H₅), 145.0, 133.8, 133.4, 133.2, 133.16, 130.2, 130.0, 129.8 (СОC₆H₅ andОSO₂C₆H₄CH₃), 77.9, 73.5, 72.4, 69.6, 62.7, 62.6, 22.9 ((CH₃)₂CH-), 22.2 ((CH₃)₂CH-), 21.6 (ОSO₂C₆H₄CH₃). HRMS (ESI⁺): m/z calcd for C₃₆H₃₆O₁₀SNa (M+Na)⁺: 683.1927, found 683.1929.

b₁. To a stirred solution of 5-O-benzoyl xylofuranose 47 (49 mg, 0.19 mmol) in anhydrous acetonitrile (2.5 ml) KHF₂ (57 mg, 0.89 mol) and boron trifluoride diethyl etherate (0.14 ml, 1.10 mmol) were added successively. The reaction mixture was stirred at room temperature for 3 h, and then poured into cooled 5% aq NaHCO₃. The aqueous phase was extracted with CHCl₃ (3x50 ml). The combined organic extracts were washed with water, dried over anh. Na₂SO₄, and evaporated to dryness. The oxazoline 49 (40 mg, 75%) was prepared as a colorless oil. (α)_D²⁰-15.9 (c 0.56, CHCl₃). M.p. 63-65 ^oC (crystallized under storing).¹Н NMR (500 MHz, CDCl₃) δ = 7.49-8.09 (m, 5H, СОC₆H₅), 6.14 (d, 1Н, J_1,2 = 5.5 Hz, Н-1), 4.86 (dd, 1Н, J_5,4 = 7.4 Hz, J_5,5′ = 11.6 Hz, Н-5), 4.82 (d, 1Н, J_2,1 = 5.6 Hz, Н-2), 4.47 (dd, 1Н, J_5′,4 = 5.1 Hz, Н-5′), 4.27 (d, 1Н, J_3,4 = 2.3 Hz, Н-3), 3.86-3.89 (m, 1Н, Н-4), 2.09 (s, 3H, NCH₃). ¹³C NMR (126 MHz, CDCl₃) δ = 168.9 (CN), 167.3 (C=O, СОC₆H₅), 100.0 (С-1), 86.6 (C-4), 76.7, 74.1 (C-2, С-3), 61.3 (С-5), 13.9 (NMe).HRMS (ESI⁺): m/z calcd for C₁₄H₁₅NO₅ (M+H)⁺: 278.1028, found 278.1025.

b₂. To a stirred solution of 1,3,5-tri-O-benzoyl-α-D-ribofuranose (50) (250 mg, 0.54 mmol) in anhydrous acetonitrile (10.0 ml) KHF₂ (156 mg, 1.99 mmol) and boron trifluoride diethyl etherate (0.39 ml, 3.08 mmol) were added successively. The reaction mixture solution was stirred at room temperature for 3.5 h, and then poured into cooled 1N aq NaOH. The oxazoline 13 (204 mg, 99%) was prepared as a colorless oil after the work-up.

c_2. To a stirred solution of ribofuranose derivative 50 (100 mg, 0.22 mmol) in anhydrous acetonitrile (4.0 ml) boron trifluoride diethyl etherate (0.16 ml, 1.26 mmol) was added. The reaction mixture solution was stirred at room temperature for 3.5 h, and then poured into cooled 2.7 ml 1N aq NaOH. The oxazoline 13 (90 mg) as yellowish oil was prepared in 65% yield estimated by ¹H NMR in CDCl₃.

3,5-Di-O-benzoyl oxazoline derivative 17 (95 mg, 0.21 mmol) was dissolved in 7 ml methanol saturated at 0 ^oC with ammonia, then reaction mixture was left for 14 h at room temperature and evaporated to dryness. The residue was chromatographed on a silica gel, using for elution chloroform, chloroform-methanol 15:1, 10:1 and 6:1 to give (47 mg, 93%) of the oxazoline 51 as oil. (α)_D²⁰-18.7 (c 0.56, MeOH). ¹Н NMR (500 MHz, CD₃OD) δ = 7.99-7.49 (m, 5H, -N=C-C₆H₅), 6.18 (d, 1Н, J_1,2 = 6.2 Hz, Н-1), 5.03 (dd, 1Н, J_2,3 = 1.3 Hz, Н-2), 4.36 (br.d, 1Н,Н-3), 3.98-4.01 (m, 1Н, Н-4), 3.49 (dd, 1Н, J_5,4 = 6.0, J_5,5′ = 11.8 Hz, Н-5), 3.44 (dd, 1Н, J_5′,4 = 6.1 Hz, Н-5′). ¹³C NMR (126 MHz, CD₃OD) δ = 168.74 (CN), 134.08, 130.01 and 128.04 (N-C₆H₅), 101.98 (С-1), 90.85 (C-4), 87.31, 77.86 (C-2, С-3), 62.93 (С-5). HRMS (ESI⁺): m/z calcd for C₁₂H₁₃NO₄ (M+H)⁺: 236.0923, found 236.0927.

The oxazoline 51 (20 mg, 0.085 mmol) was dissolved in 1.7 ml anhydrous pyridine, acetic anhydride (0.04 ml, 0.42 mmol) was added, then reaction mixture was stirred for 48 h at room temperature and then poured into a mixture of ice and water. The aqueous phase was extracted with CH₂Cl₂ (3x20 ml). The combined organic extracts were washed with water, dried over anh. Na₂SO₄, and evaporated to dryness. The residue was chromatographed on a silica gel, using for elution elution mixtures of ethylacetate-petroleum ether to give (22 mg, 80%) of the oxazoline 52 as oil. (α)_D²⁰ -4.6 (c 0.3, CHCl₃). ¹Н NMR (500 MHz, CDCl₃) δ = 7.42-8.03 (m, 5H, -N=C-C₆H₅), 6.30 (d, 1Н, J_1,2 = 6.2 Hz, Н-1), 5.32 (br.d, 1Н,Н-3), 5.04 (br.d, 1Н, J_2,3 = 1.3, J_2,1 = 6.2 Hz, Н-2), 4.26-4.33 (m, 1Н, Н-4), 4.06 (dd, 1Н, J_5,4 = 5.9, J_5,5′ = 11.8 Hz, Н-5), 4.02 (dd, 1Н, J_5′,4 = 6.1 Hz, Н-5′), 2.15 and 1.89 (2s, 3H, -COCH₃). ¹³C NMR (126 MHz, CD₃OD) δ= 170.6, 169.9 and166.5 (2-COCH₃ and CN), 132.7, 129.1, 128.8, 128.6 (N-C₆H₅), 102.2 (С-1), 86.1 (C-4), 81.2, 78.8 (C-2, С-3), 62.5 (С-5), 20.9 and 20.6 (2xCOCH₃). HRMS (ESI⁺): m/z calcd for C₁₆H₁₇NO₆ (M+Na)⁺: 3430940, found 343.0945.