A Regioselective One Pot Synthesis and Synthetic Applications Of

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A Regioselective One Pot Synthesis and Synthetic Applications of Cyanodeoxy Sugars by Cyanotrimethylsilane [1] Syed Najam-ul-Hussain Kazmia, Zaheer Ahmed3, Abdul Malik3 *, Nighat Afzab, Wolfgang Voelterc a H. E. J. Research Institute of Chemistry, University of Karachi, Karachi 75270, Pakistan b Pharmaceutical and Fine Chemical Division, P.C.S.I.R. Laboratories, Karachi 75280, Pakistan c Abteilung für Physikalische Biochemie, Physiologisch-chemisches Institut der Universität Tübingen. Hoppe-Seyler-Straße 4, 72076 Tübingen. Germany Z. Naturforsch. 50b, 294-302 (1994); received June 28, 1994 Anhydro Sugars, Cyanodeoxy Sugars, Epoxy Ring Opening, Branched Chain Pyranoses, Cyanotrimethylsilane The regioselective epoxide opening of different 2,3-anhydropyranoses by cyanotrimethyl silane is investigated. The isolated cyanodeoxy pyranoses allow easy access to the correspond ing branched-chains aminomethyl sugars by lithium aluminium hydride reduction or sugar amides by controlled acid hydrolysis.

Introduction described by them and involves initial formation Cyanodeoxy sugars assume a key role in the of C12A1CN species by the reaction of cyanotri syntheses of C-glycosyl compounds and branched- methylsilane and aluminium chloride. The reac chain sugars [2-5] besides serving as precursors tion of the C12A1CN species with oxiranes gives for most of the naturally occurring C-nucleoside a cyano-aluminated product [12] that undergoes antibiotics and their analogs [2-6], One method fra«s-metallation with cyanotrimethylsilane to give employed, amongst others, for the synthesis of trimethylsilyloxy nitrile with the regeneration of cyanodeoxy sugars involves cleavage of the oxir- the A1C13 species. An alternate mechanism is also ane ring in 2,3-anhydropyranosides by a variety of proposed [13] in which a complex is formed be nitrile containing reagents [7], The epoxides of tween the Lewis acid and the oxygen of the monocyclic sugars have a flexible half-chair con strained ether. Ring opening then occurs via a six- formation [8-10] and exist in two forms 5H0 and membered transition state in which the nucleo- °H5; trans -diaxial epoxide cleavage in these leads philic attack by the carbon of the isocyanide form in general to a binary mixture of isomeric com of trimethylsilyl cyanide occurs simultaneously pounds. Moreover, if a trans-hydroxy group is ad with chloride attack on silicon. Exchange of oxy jacent to the epoxide group, epoxide migration gen and chloride between silicon and aluminium may occur, giving several undesirable side prod then gives the product and regenerates the cata ucts [11]. A reaction which overcomes these limit lyst. In the present work we found that epoxide ing factors in the trans -diaxial opening of the ring opening in a group of 2,3-anhydro sugars with oxirane rings in 2,3-anhydro sugars with cyanotri cyanotrimethylsilane and aluminium chloride re methylsilane in presence of 1 equivalent of an sults in partial transformation to cyanodeoxy su hydrous aluminium chloride as catalyst. The role gars which did not consume periodate, and did not of aluminium chloride in controlling the ambident react with lead tetraacetate, thus indicating the reactivity of cyanotrimethylsilane and the prefer absence of a 1,2-glycol moiety. The product in ential formation of nitriles over isonitriles has al each case arises from the more stable predominant conformation of the epoxy sugar. The isomeric ready been reported in literature by Imi et al. [12]. The reaction path way of the reactants was also products were formed in trace amounts and could be eliminated easily through column chromatogra phy. Apart from the cyanodeoxy sugars the un changed anhydro sugars could also be recovered * Reprint requests to Prof. Dr. A. Malik. and recycled. The absence of trimethylsilyl ether

Dieses Werk wurde im Jahr 2013 vom Verlag Zeitschrift für Naturforschung This work has been digitalized and published in 2013 by Verlag Zeitschrift in Zusammenarbeit mit der Max-Planck-Gesellschaft zur Förderung der für Naturforschung in cooperation with the Max Planck Society for the Wissenschaften e.V. digitalisiert und unter folgender Lizenz veröffentlicht: Advancement of Science under a Creative Commons Attribution Creative Commons Namensnennung 4.0 Lizenz. 4.0 International License. S. N. Kazmi et al. • A Regioselective One Pot Synthesis 295 moiety in the products is probably due to the hy Epoxide migration was not observed in the case drolysis by the hydrogen chloride present as im of anhydro sugar (1) which has an adjacent purity in the catalyst. hydroxy group trans to the epoxide ring. The ap proach of the Lewis catalyst for co-ordination with Results and Discussion the oxirane oxygen is sterically hindered in 5 by As model compounds we synthesized benzyl- the a-oriented bulky substituent at C-l as well as 2, 3-anhydro-a-D-lyxopyranoside (1) [14], benzyl- hydrogen bonding [21], and should have resulted 2.3-anhydro-/3-L-ribopyranoside (2) [14], methyl- in exceptionally low yield of the cyanodeoxy sugar 2.3-anhydro-4,6-0-benzylidene-a-D-allopyranoside (10) if the second mechanism is operative. How (3) [15], methyl-2,3-anhydro-4,6-0-benzylidene- ever, the yield of 10 was comparable to those of a-D-mannopyranoside (4) [16], and benzyl-2,3-another sugars (Table I) which reflects that the oxir hydro-a-D-ribopyranoside (5) [17], respectively. ane ring is cleaved by C12A1CN species (mechan The anhydro sugars (1) and (2) have been shown ism 1). The time of reaction was, however, signifi by 'H NMR to exist almost entirely in the favored cantly decreased to 4h rather than 8-18 h half-chair conformation 5H0. 7rans-diaxial open required for other epoxy sugars apparently be ing leads to benzyl-3-cyano-3-deoxy-a-D-arabino- cause of the approach of C12A1CN species from pyranoside (6) and benzyl-3-cyano-3-deoxy-/3-L- the sterically less hindered direction. xylopyranoside (7), respectively. The attack by The structures of compounds 6-10 were fully cyanide at position 3 is also favoured by steric con supported by the analytical data (Table I) as well siderations as position 2 is comparatively blocked as 400 MHz *H NMR spectra. The chemical shift by the bulky substituent at C-l. The anhydro assignments were facilitated by a series of 'H ^ H sugars (3) and (4) are locked in the :’H0 confor homodecoupling experiments, 'H-'H-correlated mation by the trans -fused 4,6-O-benzylidene ring spectroscopy (COSY-45°), and 2 D-7-resolved and the cleavage gives diaxial products (8) and (9) spectra. The conformations adopted by pyranoside according to the Fürst-Plattner rule [19]. The rings in compounds (6 - 10) were determined by anhydro sugar (5) undergoes trans -diaxial cleav vicinal coupling constants and chemical shift cor age to give benzyl-3-cyano-3-deoxy-a-D-xylopyr- relations. The chemical shifts for 1-H appeared to anoside (10). In this epoxy sugar the conformation be the most helpful of all parameters in assigning during the reaction is evidently 5H0, which is stabi conformations to all five compounds. It remained lized in the transition state by hydrogen bonding fairly constant for compounds (8 - 10) and showed between the 4-hydroxy group and the ring oxygen close agreement to the a-glycosidic sugars of 4Q atom. The participation of the 5H0 conformation conformation in which this proton resonates com has already been described in the literature [20] to paratively downfield due to the equatorial orien explain the persistent formation of xylopyranoside tation. On the other hand, in sugars 6 and 7 the derivatives from this epoxy sugar. signals of 1-H appeared at comparatively upfield

Table I. Physical data and analy Com Reaction Yieldb M d c Formula Found/Calcd (%) ses3 of compounds 6-10. pound time (h) (%) C H N

6 9 59 66.60 c 13h 15n o 4 62.42 6.01 5.60 (62.46 6.07 5.62) 7 8 62 -13.04 c 13h 15n o 4 62.39 5.99 5.68 (62.46 6.07 5.62) 8 18 47 20.13 Ci5H17N 0 5 61.79 5.92 4.83 a Elemental analyses were car (61.83 5.88 4.81) ried out with a Carlo Erba Ele mental Analyzer, MOD-1106; 9 16 53 100.29 c 15h 17n o 5 61.81 5.80 4.75 b the isolated yield; c the optical (61.83 5.88 4.81) rotations were measured on a 10 4 55 25.10 c 13h 15n o 4 62.43 6.03 5.64 Schmidt and Haensch Polar- (62.46 6.07 5.62) tronic-D Polarimeter using chloro form as solvent. 296 S. N. Kazmi et al. • A Regioselective One Pot Synthesis

(H 3C)3SiCN + A1C1, (H 3Q 3S1CI + C12 A1CN

C1->A1-C=N RI / V Y

C = N-A1C1;

w ork-up (2 ) R 1 = H, R 2 = OH

(7) R = H, R = OH

work-up

o a ^ P h

Scheme 1 (8 ) r' = cn, r : = oh (9) r' = oh ,r 2 = c n S. N. Kazmi et al. ■ A Regioselective One Pot Synthesis 297

Tab. II. !H NMR data 3 of compounds 6- 10.

Compound Conformation Pyranoside ring ArH

6 1C 4.67 (1 H, d, 1-H), 4.19 (1 H, dd, 5-Ha), 7.34-7.28 (5H, m) 4.69 (2H, dd, C H .-Ph), 3.90 (1 H, dd, 5-Hb), 3.69 (1 H, m, 4-H), 3.66 (1 H, dd, 2-H), 2.89 (1 H, dd, 3-H) 7 1C 4.64 (1 H, d, 1-H), 4.21 (1 H, dd, 5-Ha), 7.35-7.28 (5H, m) 4.59 (2H, dd, C H ,-Ph), 3.98 (1 H, dd, 5-Hb), 3.87 (1 H, m, 4-H), 3.60 (1 H, dd, 2-H), 2.98 (1 H, dd, 3-H) 8 C l 5.01 (1H, d, 1-H), 4.23 (1H, dd, 6-Ha), 7.53-7.39 (5H, m) 9.38 (1H, s, HC-Ph), 4.05 (1 H, dd, 6-Hb), 3.91 (1 H, m, 5-H), 3.46 (3 H, s, OCH,) 3.72 (1 H, dd, 4-H), 3.51 (1 H, dd, 3-H), 3.10 (1H, dd, 2-H) 9 C l 5.12 (1H, d, 1-H), 4.05 (1H, dd, 6-Ha), 7.53-7.34 (5H, m) 10.02 (1H, s, HC-Ph), 3.92 (1 H, dd, 6-Hb), 3.86 (1 H, m, 5-H), 3.37 (3 H, s, OCH3) 3.71 (1 H, dd, 4-H), 3.61 (1 H. dd, 2-H), 2.91 (1H, dd, 3-H) 10 C l 5.06 (1H, d, 1-H), 4.01 (1H, dd, 5-Ha), 7.33-7.27 (5H, m) 4.69 (2H, dd, CF^-Ph), 3.87 (1 H, dd, 5-Hb), 3.70 (1 H, m, 4-H), 3.59 (1 H, dd, 2-H), 3.10 (1 H, dd, 3-H)

Coupling constants of compounds 6-10.

Compound J 1,2 J 23 •^3.4 J 4.5 J 4,5 ' • I 5,6 J 5,6' ^ 6 ,6 ' • I 5 ,5 ' Ph-C H , 2 6 8.16 9.03 3.12 3.90 2.93 ___ 9.11 11.12 7 8.32 9.98 9.07 9.31 9.98 --- 9.47 10.01 8 2.65 2.52 3.21 9.28 - 4.05 4.23 10.72 -- 9 2.81 2.35 3.62 8.76 - 3.12 2.07 10.20 -- 10 2.12 9.18 9.91 8.98 3.87 -- - 9.42 11.54

a At 400 MHz on a Bruker AM-400 spectrometer. Chemical shifts are quoted in <3 units relative to Me 4Si. positions indicating axial orientation and hence Some interesting sugar derivatives have also 1C4 conformation. Further confirmation was pro been synthesized by simple one pot reactions on vided by the values of Ji 2, J23, ^3,4 , and J4 5, re cyanodeoxy sugars (6-10). For instance refluxing spectively. The vicinal protons having diaxial re with lithium aluminium hydride in tetrahydro- lationship invariably showed larger coupling furan for 8 h resulted in theoretical conversion to constants ranging from 8-12 Hz. A summarized the corresponding aminomethyl sugars (11-15). account of the *H NMR spectra of all these com In the IR spectra the C-N stretching vibrations pounds is given in Table II. disappeared and bands at 3400-3300 cm - 1 and The 13C NMR spectra of these compounds were 1600-1590 cm - 1 for NH 2 group appeared. The 'H also recorded not only to lend further support to NMR spectra showed an additional 2H broad the assigned structures, but also because of the fact multiplet in the range of 2.83-2.94 ppm for that the 13C NMR data of cyanodeoxy sugars are CH 7NH 9 and another 2H multiplet in the range not frequently available in the literature. The as of 1.89-3.20 ppm which disappeared on shaking signment were made by calculation of theoretical with D20 and could be assigned to the amino values as well as 'H - 13C correlated spectroscopy group. In each compound, the multiplicity of the (heterocosy) and presented in Table III. proton on the carbon carrying the aminomethyl 298 S. N. Kazmi et al. • A Regioselective One Pot Synthesis

Table III. 13C NMR data3 of compounds 6-10.

Compound C-l C-2 C-3 C-4 C-5 C-6 CN Ph-C o c h 3 ArC

6 102.03 70.98 40.97 69.89 67.28 120.13 70.96 137.04 (C-l'), 128.90 (C-2'), 128.17 (C-3'), 127.98 (C-4') 7 93.71 70.21 41.23 71.27 72.93 120.41 70.48 136.93 (C-l'), 128.90 (C-2'), 128.61 (C-3'), 128.20 (C-4') 8 99.03 41.39 68.17 75.68 57.59 69.12 120.38 101.57 55.13 136.03 (C-l'), 127.80 (C-2'), 125.79 (C-3'), 128.21 (C-4') 9 99.17 69.13 40.78 75.71 57.83 68.97 121.03 101.31 54.98 136.27 (C-l'), 127.70 (C-2'), 125.84 (C-3'), 128.69 (C-4') 10 94.18 71.67 41.18 70.19 62.42 120.46 71.81 136.94 (C-l'), 129.10 (C-2'), 128.75 (C-3'), 128.35 (C-4')

a At 100 MHz on a Bruker AM-400 spectrometer. Chemical shifts are in ppm from Me4Si.

group was changed from double doublet to mul- tential compounds. On the other hand, controlled tiplet. It is interesting to note that the branched- acid hydrolysis of 6-10 with 20% aqueous hydro chain amino sugars constitute the essential part of chloric acid by heating at 50° for 1 h afforded a some highly effective antibiotics like vancomycin mixture of products from which sugar amides (16- [22] and everninomicin [23], The present strategy 20) could be separated by p.I.e. and characterized. provides a simple and general route to these po In each case one more product was obtained

OCH2Ph

R3 b

(11) R 1 = R4 = R6 = H, R2 = R5 = OH, R3 = CH2-NH2 (13) R 1 = R4 = H, R2 = CH2-NH2, R3 = OH (12) R1 = R4 = R5 = H, R2 = R6 = OH, R3 = CH2-NH2 (14) R 1 = R4 = H, R2 = OH, R3 = CH2-NH2 (15) R 1 = R5 = OH, R2 = R3 = R6 = H, R4 = CH2-NH2 (16) R 1 = R4 = R6 = H, R2 = R5 = -OH. R3 = CO-NH2 (17) R1 = R4 = R5 = H, R2 = R6 = OH, R3 = CO-NH2 (20) R1 = R5 = OH, R2 = R3 = R6 = H, R4 = CO-NH2

Scheme 2 (18) R 1 = R4 = H, R2 = CO-NH2, RJ = OH (19) R1 = R4 = H, R2 = OH, R3 = CO-NH2 S. N. Kazmi et al. ■ A Regioselective One Pot Synthesis 299

Table IV. Physical data, FDMS and Com- FDMSb Formula Yieldc [a]od Found/Calcd (%) analyses3 of compounds 11-20. pound C H N

11 253 C13H19N 0 4 62 12.65 61.68 7.60 5.51 (61.63 7.56 5.53) 12 253 c 13h 19n o 4 61 -6.50 61.60 7.58 5.52 (61.63 7.56 5.53) 13 295 c 15h 21n o 5 67 12.71 60.88 7.23 4.80 (60.99 7.17 4.75) 14 295 c 15h 21n o 5 64 15.17 60.81 7.21 4.69 (60.99 7.17 4.75) 15 253 C i3H19N 0 4 62 12.78 61.58 7.50 5.58 (61.63 7.56 5.53) 16 267 c 13h 17n o 5 21 20.01 58.38 6.43 5.21 (58.40 6.41 5.24) a Elemental analyses were carried out with a Carlo Erba Elemental 17 267 c 13h 17n o 5 24 25.18 58.43 6.44 5.23 Analyzer, MOD-1106; b FDMS were (58.40 6.41 5.24) recorded on Finnigan MAT-312 18 309 q 5h 19n o 6 21 20.13 58.20 6.16 4.56 mass spectrometer connected to (58.23 6.19 4.53) PDP 11/34 (DEC) computer system; c the yields are calculated on the 19 309 c 15h 19n o 6 23 15.38 58.19 6.15 4.58 basis of starting cyanodeoxy sugars; (58.23 6.19 4.53) d the optical rotations were meas 20 267 c 13h 17n o 5 20 15.96 58.38 6.37 5.26 ured on a Schmidt and Haensch (58.40 6.41 5.24) Polartronic-D Polarimeter using chloroform as solvent. which showed reducing properties and appeared (!H 400.13 and 13C 100.60 MHz) spectrophotome to be the corresponding dealkylated derivatives ters with TMS as internal standard. Field desorp of 16-20. However, these could not be obtained tion mass spectra were determined on a Finnigan pure due to hygroscopic nature and unstability at MAT-312 spectrometer coupled with a PDP 11/34 computer system while optical rotations were room temperature. The disappearance of the measured on a Schmidt and Haensch Polar- C-N stretching in the IR spectra was ac tronic-D Polarimeter. The physical data, ’H and companied by appearance of bands due to C=0 13C NMR spectra of various compounds are given (1655-1645 cm“1) and NH2 (3520-3400 and in Tables I-IV . 1615-1590 cm“1). The !H NMR spectra showed an additional 2H broad singlet in the range of 6.20-6.95 ppm which disappeared on shaking with Benzyl-3-cyano-3-deoxy-a-D-arabinopyranoside (6) D20 and could be assigned to CONH,. A solution of benzyl-2,3-anhydro-a-D-lyxopyranoside (1) (0.22 g, 1 mmol) in dry dichlorome- Experimental thane (4 ml) was treated with cyanotrimethylsilane Cyanotrimethyl silane, aluminium chloride and (0.3 ml, 2.25 mmol) at -10 °C followed by rapid lithium aluminium hydride were purchased from addition of anhydrous aluminium chloride (0.13 g, Aldrich, Fluka and E. Merck, respectively. Sol 1 mmol). Refluxed the reaction mixture for 4 h on vents were purified by standard methods and dried boiling water bath. Further heating results in the if necessary. Reagents were used in commercial formation of a complex mixture of side products. quality. Thin layer chromatographic analyses were The reaction mixture was hydrolyzed with water carried out on preparative glass plates covered and extracted with dichloromethane. It was then with silica gel 60F254 (E. Merck). The spots were washed with water, dried over anhydrous sodium detected by UV (254 nm) and in addition to that sulfate, and the solvent was removed under re by spraying with orcinol solution. IR spectra were duced pressure. The oily residue thereby obtained obtained on a JASCO IRA-1 spectrophotometer; was chromatographed over silica gel using the ’H NMR spectra were scanned on Bruker AM 300 solvent system chloroform-methanol (9.8:0.2) to (!H 300.13 and 13C 75.43 MHz) and AM 400 yield the unreacted epoxy sugar (1) and the com 300 S. N. Kazmi et al. ■ A Regioselective One Pot Synthesis pound 6. FDMS: m/z = 249 (M+); vmax (KBr)/ above for 6. FDMS: m/z = 249 (M+); vmax (KBr)/ cm“1 = 3560 (OH) and 2230 (CN). cm -1 = 3540 (OH) and 2240 (CN).

Benzyl-3-aminomethyl-3-deoxy-a-D-arabino- Benzyl-3-cyano-3-deoxy-ß-L-xylopyrcinoside (7) pyranoside (11) A solution of benzyl-2,3-anhydro-/?-L-ribo- A solution of benzyl-3-cyano-3-deoxy-a-D-ara- pyranoside (2) (0.44 g, 2 mmol) in dry dichloro- binopyranoside (6) (15 mg, 0.06 mmol) in tetra- methane (8 ml) was treated with cyanotrimethyl- hydrofuran (8 ml) was added in portions to the silane (0.6 ml, 4.5 mmol) at -10 °C followed by stirred solution of lithium aluminium hydride in rapid addition of anhydrous aluminium chloride ether (5 ml, 5% w/v) which effervesced at each (0.26 g, 2 mmol). The reaction mixture was re addition. The stirred suspension was refluxed for fluxed for 8 h on a boiling water bath and then 8 h. Ethanol was added dropwise to decompose proceeded according to the procedure described the excess of hydride and the solution, diluted with above for 6. FDMS: m/z = 249 (M+); vmax (KBr)/ ether, was shaken with 10% aqueous sodium hy cm -1 - 3540 (OH) and 2240 (CN). droxide. The ethereal layer was separated from the aqueous layer. The combined ethereal extracts Methyl-2-cyano-2-deoxy-4,6-0-benzylidene-a-D- were washed with water, dried over anhydrous so altropyranoside (8) dium sulfate, evaporated in vacuum and chroma tographed over silica gel using the solvent system A solution of methyl-2,3-anhydro-4,6-0-benzyl- chloroform-methanol (9.7:0.3) to yield a basic idene-a-D-allopyranoside (3) (0.264 g, 1 mmol) in syrup (11). FDMS: m/z = 253 (M+); vmax (KBr)/ dry dichloromethane (4 ml) was treated with cm“1 = 3410, 3380 and 1600 (NH2); *H NMR cyanotrimethylsilane (0.3 ml, 2.25 mmol) at -10 °C (CDC13): d = 2.84 (m, 2H, CH 2 -NH 2 ) and 3.1 (m, followed by rapid addition of anhydrous aluminium 2H, NH2). chloride (0.13 g, 1 mmol). The reaction mixture was refluxed for 18 h on a boiling water bath and Benzyl-3-aminomethyl-3-deoxy-ß-L-xylopyranoside then proceeded according to the procedure de (12) scribed above for 6. FDMS: m/z = 291 (M+); A solution of benzyl-3-cyano-3-deoxy-/?-L-xylo- vmax (KBr)/cm_1 = 3520 (OH) and 2240 (CN). pyranoside (7) (25 mg, 0.1 mmol) in tetrahydrofuran (10 ml) was added in portions to a 5% w/v Methyl-3-cyano-3-deoxy-4,6-0-benzylidene-a-D- ethereal solution of lithium aluminium hydride altropyranoside (9) (5 ml) and then proceeded according to the pro cedure described above for 11. FDMS: m/z = 253 A solution of methyl-2,3-anhydro-4,6-0-benzyl- (M+); vmax (KBrVcm-1 = 3420, 3380 and 1590 idene-a-D-mannopyranoside (4) (0.264 g, 1 mmol) (NH2); NMR (CDC13): (3 = 2.90 (m, 2H, in dry dichloromethane (4 ml) was treated with CH 2 -N H 2) and 2.65 (m, 2H, NH2). cyanotrimethylsilane (0.3 ml, 2.25 mmol) at -10 °C followed by rapid addition of anhydrous alu Methyl-2-aminomethyl-2-deoxy-4,6-0-benzylidene- minium chloride (0.13 g, 1 mmol). The reaction a-D-altropyranoside (13) mixture was refluxed for 16 h on a boiling water bath and then proceeded according to the pro A solution of methyl-2-cyano-2-deoxy-4,6-0- cedure described above for 6. FDMS: m/z = 291 benzylidene-a-D-altropyrano-side (8) (15 mg, (M+); vmax (K B^/cm “1 = 3600 (OH) and 2230 0.05 mmol) in tetrahydrofuran (8 ml) was added in (CN). portions to a 5% w/v ethereal solution of lithium aluminium hydride (4 ml) and then proceeded ac cording to the procedure described above for 11 Benzyl-3-cyano-3-deoxy-a-D-xylopyranoside (10) to yield compound 13. FDMS: m/z = 295 (M+); A solution of benzyl-2,3-anhydro-a-D-ribo- vmax (KBr)/cm_1 - 3400, 3360 and 1600 (NH2); 'H pyranoside (5) (0.22 g, 1 mmol) in dry dichloro NMR (CDCI3): (3 = 2.94 (m, 2H , C Fh-N H z) and methane (4 ml) was treated with cyanotrimethyl 2.43 (m, 2H , NH2). silane (0.3 ml, 2.25 mmol) at -10 °C followed by rapid addition of anhydrous aluminium chloride Methyl-3-aminomethyl-3-deoxy-4,6-0-benzylidene- (0.13 g, 1 mmol). The reaction mixture was re a-D-altropyranoside (14) fluxed for 9 h on a boiling water bath and then A solution of methyl-3-cyano-3-deoxy-4,6-0- proceeded according to the procedure described benzylidene-a-D-altropyrano-side (9) (12 mg, S. N. Kazmi et al. • A Regioselective One Pot Synthesis 301

0.04 mmol) in tetrahydrofuran (6 ml) was added in chloric acid (25 ml) and then proceeded according portions to a 5% w/v ethereal solution of lithium to the procedure described above for 16 to get aluminium hydride (3 ml) and then proceeded ac compound 17. FDMS: m/z = 267 (M+); vmax (KBr)/ cording to the procedure described above for 11 cm -1 = 3490, 3400 and 1600 (NH2) and 1650 (CO); to yield compound 14. FDMS: m/z - 295 (M+); *H NMR (CDC13): <3 = 6.32 (br. s, 2H, C O -N H ,). vmax (KBr)/cm_1 = 3400, 3390 and 1600 (NH2); 'H NMR (CDC13): d = 2.83 (m, 2H, CH 2 -N H 2) and Methyl-2-carboxamido-2-deoxy-4,6-0-benzylidene- 1.89 (m, 2H, NH2). a-D-altropyranoside (18) Benzyl-3-aminomethyl-3-deoxy-a-D-xylo- Methyl-2-cyano-2-deoxy-4,6-0-benzylidene-a-D- pyranoside (15) altropyranoside (8) (20 mg, 0.06 mmol) was re A solution of benzyl-3-cyano-3-deoxy-a-D-xylo- acted with 20% hydrochloric acid (14 ml) and then pyranoside (10) (20 mg, 0.08 mmol) in tetrahydro proceeded according to the procedure described furan (10 ml) was added in portions to a 5% w/v above for 16 to get compound 18. FDMS: m/z - ethereal solution of lithium aluminium hydride 309 (M+); vmax (KBr)/cm_1 = 3500, 3420 and 1600 (4 ml) and then proceeded according to the pro (NH2) and 1655 (CO); !H NMR (CDC13): (3 = 6.85 cedure described above for 11 to yield compound (br. s, 2H, CO-NFh). 15. FDMS: m/z = 253 (M+); vmax (KBO/cm“1 = 3410, 3390 and 1600 (NH2); 'H NMR (CDC13): <3 = Methyl-3-carboxamido-3-deoxy-4,6-0-benzylidene- 2.88 (m, 2H, C F h -N H ^ and 2.20 (m, 2H, NH2). a-D-altropyranoside (19)

Benzyl-3-carboxamido-3-deoxy-a-D-arabino- Methyl-3-cyano-3-deoxy-4,6-0-benzylidene-a-D- pyranoside (16) altropyranoside (9) (25 mg, 0.086 mmol) was re acted with 20% hydrochloric acid (25 ml) and then Benzyl-3-cyano-3-deoxy-a-D-arabinopyranoside proceeded according to the procedure described (6) (20 mg, 0.08 mmol) was reacted with 20% above for 16 to get compound 19. FDMS: m/z = hydrochloric acid (15 ml) at 50 °C for 1 h. The re 309 (M+); vmax (KBr)/cm_1 = 3500, 3420 and 1600 action mixture was then neutralized and extracted (NH2) and 1650 (CO); 'H NMR (CDC13): <3 = 6.20 thrice with dichloromethane. The organic phase (br. s, 2H , C O -N H 2). was separated, dried over anhydrous sodium sul fate, evaporated at reduced pressure and purified by p.I.e. using chloroform-methanol (9.5:0.5) to Benzyl-3-carboxamido-3-deoxy-a-D-xylo- ( ) get the oily product 16. FDMS: m/z = 267 (M+); pyranoside 20 vmax (KBr)/cm-1 = 3520, 3410 and 1615 (NH2) and Benzyl-3-cyano-3-deoxy-a-D-xylopyranoside 1650 (CO); 'H NMR (CDC13): d = 6.61 (br. s, 2H , (10) (30 mg, 0.12 mmol) was reacted with 20% C O -N Fh). hydrochloric acid (25 ml) and then proceeded ac cording to the procedure described above for 16 Benzyl-3-carboxamido-3-deoxy-ß-L-xylopyranoside to get compound 20. FDMS: m/z = 267 (M+); (17) vmax (KBr)/cm_1 = 3500, 3420 and 1590 (NH2) and Benzyl-3-cyano-3-deoxy-/?-L-xylopyranoside (7) 1645 (CO); 'H NMR (CDC13): (3 = 6.95 (br. s, 2H, (30 mg, 0.12 mmol) was reacted with 20% hydro CO-NH2). 302 S. N. Kazmi et al. • A Regioselective One Pot Synthesis

[1] S. N. H. Kazmi, Z. Ahmed, A. Q. Khan, A. Malik, 10] B. Ottar, Acta Chem. Scand. 1, 283 (1947). Synthetic Communications 18(2), 151 (1988). 11] W. H. G. Lake, S. Peat, J. Chem. Soc. 1939, 1069. [2] S. Hanessian, A. G. Pernet, Adv. Carbohydr. Chem. 12] K. Imi, N. Yanagihara, K. J. Utimoto, J. Org. Chem. Biochem. 33, 111 (1976). 52, 1013 (1987). [3] G. D. Daves, C. C. Cheng, Prog. Med. Chem. 13, 13] J. C. Mullis, W. P. Weber, J. Org. Chem. 47, 2873 303 (1976). (1982). [4] J. S. Brimacombe, in “Carbohydrate Chemistry”, 14] W. Kowollik, A. Malik, N. Afza. W. Voelter, J. Org. Chem. Soc. Specialist Periodical Report 9, 99 (1977) Chem. 50, 3325 (1985). and previous reports. 15] G. J. Robertson, C. F. Griffith, J. Chem. Soc. 9, [5] W. A. Szarek, D. M. MTP Vyas, International Re 1196 (1935). view of Science, Organic Chemistry, Series Two, 16] D. R. Hicks, B. F. Reid, Synthesis 1974, 203. Vol. 7, Carbohydrates, ed. G. O. Aspinall, Butter 17] J. G. Buchanan, D. M. Clode, N. Vethaviyasar, J. worth, London (1976), p. 89; W. A. Szarek, ibid, Chem. Soc., Perkin Trans. I, 1976, 1449. Series One (1973), p. 17. 18] J. G. Buchanan, R. Fletcher, K. Parry W. A. [6] M. S. Poonian, E. F. Nowoswiat, J. Org. Chem. 45, Thomas, J. Chem. Soc. B. 377 (1969). 203 (1980). 19] W. G. Overend, G. Vaughan, Chem. and Ind. (Lon [7] R. H. Hall, K. Bischofberger, A. J. Brink, O. G. de don), 1955, 995. Villiers, A. Jordaan, J. Chem. Soc. Perkin I, 3, 781 20] S. Peat, Adv. Carbohyd. Chem. 2, 37 (1946); F. H. (1979); N. R. Williams, Chem. Commun. 1967, 1012; Newth, Q. Rev. (London) 13, 30 (1959). B. E. Davison, R. D. Guthrie, J. Chem. Soc. Chem. 21] N. Afza, A. Malik, W. Voelter, J. Chem. Soc. Perkin Commun. 1968, 1273 and J. Chem. Soc. Perkin I, I, 1983, 1349. 1992, 658; F. G. De las Heras, A. S. Felix, A. Calvo- 22] R. M. Smith, A. W. Johnson, R. D. Guthrie, J. Chem. Mateo, P. Fernändez-Resa, Tetrahedron 41, 3867 Soc. Chem. Commun. 1972, 361. (1985). 23] J. S. Brimacombe, L. W. Doner, J. Chem. Soc. Perkin [8] D. H. Buss, L. Hough, L. D. Hall, J. F. Manville, I, 1974, 62. Tetrahedron 21, 69 (1965). [9] W. R. Jackson, A. Zurqiyah, J. Chem. Soc. B., 49 (1966).

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