2168 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA J. Org. zyxwvu KJIHGF Chem. 1984,49, zyxwv IHGFE 2168-2174 (12). A solution of 8 (300 mg, 0.53 mmol) and ethyl propiolate (600 mg, 6 mmol) in toluene (4 mL) was pyrolyzed in a sealed tube for 1 h at 220 “C. Excess ethyl propiolate was removed by fast chromatography on a silicagel suction column, and the residue zyxwvu BA was separated by zyxwvutsrq CBA using high-performance liquid chromatography (Jobin-Yvon Chromatospac Prep 100, column diameter 8 cm, silicagel from Merck, zyxwvutsrq CBA art. 7736; eluted with 30% ethyl acetate in dichloromethane at 8 bar, 35 mL/min; detection with RI). In this way 0.160 g (48%) of compound 11 and 0.051 g (16%) of the 4-position substituted isothiazole 12 was obtained. Isothiazole 11 (oil): IR (oil film) 1740 cm-’ (CO); ‘H NMR (CDC13) 6 8.1-7.85 (m, 6, Ar H), 7.80 zyxwvuts EDCBA (e, 1, H4), 7.60-7.20 (m, 9, 1, HI,), 4.9-4.6 (m, 3, H4,, H5,, H5”), 4.35 (9, 7 Hz, 2, CHz), 1.26 Ar H), 6.1 (t, 4.5 Hz, 1, Hy), 5.90 (t, 4.5 Hz, 1, H3,), 5.47 (d, 5 Hz, (t, 7 Hz, 3, CH3); 13C NMR (CDC13) 6 1.68 (C3), 166.0-165.2 (COOPh), 159.5 (COOEt), 158.3 (C5), 133-128 (Ar C), 125.9 (C1), 80-63 (ribosyl C), 61.8 (CH2), 13.9 (CH,); mass spectrum, m l e 601, 573, 556, 479, 357, 105; exact mass calcd for C32H27NOsS 601.141, found 601.141 * 0.001. Isothiazole 12 (oil): ‘H NMR (CDCl,) 6 9.2 zyxwvut EDCBA (8, 1, H,), 8.1-7.8 (m, 6, Ar H), 7.5-7.2 (m, 9, Ar H), 6.2 (m, 3, HIT, HZr, H34, 4.8 (m, 3, H4,, H,,, H,,,), 4.3 (q,6 Hz, 2, CHz), 1.26 (t, 6 Hz, 3, CH,); mass spectrum, m / e 601,584,572,556,479,357,105; exact mass calcd for C92H27NOgS, 601.141, found 601.140 * 0.001. Ammonolysis of Compounds 10-12: Preparation of the Amides 3-5. A solution of compounds 10-12 (0.2 mmol) in methanol (2 mL) saturated with ammonia was stirred at room temperature for 80 h. After every 24-h period the solvent was evaporated and replaced by freahly prepared methanolic ammonia. After the reaction was completed, the solvent was evaporated and the residue was taken up in water (3 mL) and washed (3 times) with chloroform. The water layer was freeze-dried and the residue was recrystallized from 2-propanol to yield the very hygroscopic amides 3-5. 3-@-~-Ribofuranosyl-1,2,4-thiadiazole-5-carboxamide (3): yield 60%; mp 155-156 “C; IR (oil film) 3310 (OH, NH2), 1675 cm-’ (CO); ‘H NMR (DzO) S 5.17 (d, J = 5.6 Hz, 1, HI,), 4.48 (dd, 2.3, and 6.4 Hz, 1, H40, 3.87 (dd, 2.3 and -12.5 Hz, 1, H5,), 3.77 80.8,84.9 (ribosyl C), 161.2 (CONHz), 174.6 (C3), 184.5 (C,); mass spectrum (+4Me3Si), m / e 549,534,459,446,356,316,256,244, 230,217,159,158,129,103,73. Anal. Calcd for CBHllN305S: C, 36.78; H, 4.24; N, 16.08. Found C, 36.61; H, 3.90; N, 15.66. 3-@-~-Ribofuranosylisothiazole-5-carboxamide (4): yield 55%; mp 135-137 “C; IR (KBr) 3310 (OH, NHz), 1670 cm-’ (CO); and 5.1 Hz, 1, H2,), 4.18 (dd, 5.1 and 4.7 Hz, 1, H3,), 4.12 (ddd, 5.6 and 5.3 Hz, 1, Hzt), 4.29 (t, J = 5.3 Hz, 1, H3,), 4.17 (ddd, 5.3, (dd, 6.4 and -12.5 Hz, 1, H5u); NMR (DzO) 6 61.6, 71.2, 79.2, ‘H NMR (DzO) 6 7.8 ( ~ , 1 , H4), 5.0 (d, 6.4 Hz, 1, Hi,), 4.3 (dd, 6.4 4.7, 3.3, and 5.1 Hz, 1, H4,), 3.83 (dd, 3.3 and -12.5 Hz, 1, H5,), 3.74 (dd, 5.1 and -12.5 Hz, 1, HB); mass spectrum (+4Me3Si) m / e 548,533,458,445,368,355,315,255,230,229,227,217,157,103, 73. Anal. Calcd for CsHlzNz05S: C, 41.53; H, 4.65; N, 10.76. Found:C, 41.91; H, 5.03; N, 10.40. 3-j3-~-Ribofuranosylisothiazole-4-carboxamide (5): yield 58%; mp 89-90 “C; the product decomposed on attempted pu- rification preventing proper combustion analysis, but it was stable in aqueous solution or in vacuum; IR (KBr) 3300 (OH, NHz), 1675, 1620 cm-’ (CO); ‘H NMR (DzO, MeOD) 6 9.41 (8, 1, H& 5.45 (d, 4.16 (ddd, 5.6, 3.3, and 5.1 Hz, 1, H4J, 3.89 (dd, 3.3 and -12.4 Hz, 1, H50, 3.77 dd, 5.1 and -12.4 zyxw Hz, 1, H5J; mass spectrum (+3Me3Si), m l e 476, 461, 386,296, 283, 217,73. Acetalization of Compounds 3 and 4. Compound 3 (4) (10 mg), 1 mL of dimethoxypropane, and a pinch of p-toluenesulfonic acid was stirred at room temperature for 30 min. The mixture was placed directly on a preparative thin layer plate (silicagel) and eluted zyxwv BA with 2 % methanol in ethyl acetate to yield the desired compound as a clean, slightly yellow oil. (2’,3’- 0 -Isopropylidene)-8-D--ribofuranosyl- l,2,4-thiadia- zole-5-carboxamide (14): yield 8 mg; ‘H NMR (DzO) 6 5.34 (d, 4 Hz, 1, Hlf), 5.28 (dd, 4 and 6.5 Hz, 1, HZ3, 4.93 (dd, 6.5 and 3 Hz, 1, H30, 4.38 (td, 3 and 7 Hz, 1, H4.), 3.65 (m, 2, H, and H,,), 3-(2’,3’-0 -1sopropylidene)-@-D-ribofuranosylisothiazole- 5-carboxamide (15): yield 5 mg; ‘H NMR (CDC13) 5.16 (d, 4 Hz, 1, H13, 4.89 (dd, 4 and 6.5 Hz, 1, Hz,), 4.86 (dd, 6.5 and 2.5 Hz, 1, H3,), 4.37 (m, 1, H4,), 3.66 (m, 2, H5, and H,”), 1.64 (s, 3, Acknowledgment. We thank the “Fonds voor Kol- lektief Fundamenteel Onderzoek”, the Ministry of Scien- tific Programming, and the “Onderzoeksfonds K.U. Leuven” for financial support. We are indebted to the NFWO (D.B.) and IWONL (J.D.) for a research grant. We thank Prof. E. De Clercq (Rega Institute, KULeuven) for the biological tests, Dr. F. Compernolle and R. De Boer for mass spectral analyses, Dr. S. Toppet for NMR anal- yses, and Dr. J. Vlieghe, R. Matthe, and P. Valvekens for technical assistance. Registry NO. 3,89873-16-5; 4, 89873-17-6; 5, 89873-18-7; 6, 23316-67-8; 7, 89873-10-9; 8, 89873-12-1; 9, 89873-21-2; io, m373-13-2; 11, w m - 1 4 - 3 ; 12, m873-15-4; 14, 89873-19-8; 15, 5 Hz, 1, HI,), 4.48 (dd, 5 and 5.6 Hz, 1, HT), 4.16 (t, 5.6 Hz, 1, Hy), 1.61 (5, 3, CH3), 1.41 (9, 3, CH3). CH3), 1.40 (9, 3, CH3). 89873-20-1; ribavirin, 36791-04-5; 2,5-anhydro-3,4,6-tri-o- benzoyl-D-altronamide, 89873-11-0; ethyl cyanoformate, 623-49-4; ethyl propiolate, 623-47-2; ClSCOCl, 2757-23-5. Use of D - R i b o n o l a c t o n e in Organic Synthesis. 2. Scope and Utility Shin-Yih Chen and Madeleine M. JoulliB* Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 Received December 2, 1983 The scope and utility of D-ribonolactone (1) as a chiral template for the synthesis of optically active y-lactones which are important precursors for many natural products are discussed. The regio- and stereoselective func- tionalization of 1 is examined. Chiral y-lactones are important precursors in natural product syntheses. These compounds have been obtained either from the cyclization of acyclic starting materials, such as the stereoselective iodoladonization of unsaturated 3-hydroxy acids,l or from sugars such as D-ribofuranose’ (1) Chamberlin, A. R.; Dezube, M.; Dussault, P. Tetrahedron Lett. ( 2 ) Hanessim, S.; Haskell, T. H. J. Heterocycl. Chem. 1964, I , 55. 1981,22, 4611. 0022-3263 / 841 1949-2 168$01.50 / 0 or D-glu~osamine.~ The concept of using“chiral templates” derived from carbohydrates has been ingeni- ously and widely used in ~ynthesis.~ Most efforts in this area have traditionally focused on sugars such as D-ribose, D-glucose, etc. Manipulations involving carbohydrates, (3) Hecht, S. M.; Rupprecht, K. M.; Jacobs, P. M. J . Am. Chem. SOC. (4) For a summary, see: Hanessian, S. Acc. Chem. Res. 1979,12, 159. 1979, 101, 3982. 0 1984 American Chemical Society