ChemInform Abstract: Approaches to the Synthesis of Lincosamine, a Derived Portion of the Antibiotic Lincomycin

Autor: Robert V. Stick, L. M. Engelhardt, D. M. G. Tilbrook, Allan H. White, Brian W. Skelton
Rok vydání: 2010
Předmět:
Zdroj: ChemInform. 22
ISSN: 0931-7597
0004-9425
DOI: 10.1002/chin.199104330
Popis: A variety of approaches towards the synthesis of lincosamine, a derived portion of the antibiotic lincomycin, are reported. Initial approaches involved the intramolecular delivery of a nitrogen atom (trichloroacetimidate, trichloroacetylcarbamate, carbamate, 2-amino-2phenylacetate) attached to 0 4 onto C6 of a 6,7-anhydrooctoside. Later approaches, albeit more direct but again largely unsuccessful, involved the Sharpless titanium(1v)-mediated nucleophilic opening of a suitable 6,7-anhydrooctose, and the Sharpless oxyamination and the aziridination of suitable octenoses. As an aid to the structure elucidation of several compounds encountered in this work, single-crystal X-ray structure determinations are reported for methyl 6,7-anhydro-2,3-diO-benzyl-8-deoxy-oc-~-threo-~-galacto-octopyranoside, methyl 6,7-anhydro-2,3-di-0-benzyl-8deoxy-a-D-threo-D-gluco-octopyranoside and 7-azido-7-deoxy-l,2:3,4-d1-0-isopropylidene-/3-~erythro-D-galacto-octose. In the preceding paper we outlined the syntheses of various octenoses (1)-(4) as potential substrates for the synthesis of lincosamine (3, a derived portion of the antibiotic lincomycin.' This paper describes firstly our attempts to convert the alcohol (I), via an intermediate such as (6), into lincosamine ( 9 , and concludes with approaches from the alkenes (2)-(4) to the same target molecule. For the synthesis of an intermediate such as (6) we needed to prepare initially the epoxide (7), and two routes were available. Epoxidation of the alkene (8) followed by removal of the protecting group at 0 4 could formally lead to Stick, R. V., and Tilbrook, D. M. G., Aust. J. Chem., 1990, 43, 1643. 0004-9425/90/101657$03.00 L. M. Engelhardt et aL (7), whereas epoxidation of the alkene (I) , taking advantage of the possible directing effect of the hydroxy group at ~ 4 , ~ could lead directly to the same epoxide (7). Thus, treatment of the alkene (8) with m-chloroperbenzoic acid gave a mixture of two epoxides which were separable by flash chromatography. The major product, formed in 57% yield, was the unwanted P-L-threo epoxide (9); the required a-D-threo epoxide (10) was obtained in only 17% yield. The assignment of structure to (9) and (10) was based on 13c n.m.r. spectroscopy and comparison with related epoxides (see below): for (9), C6 resonated at 6 54 .39 and C7 at 57.28, whereas the corresponding resonances in (10) were at 51.18 and 5 8 . 7 0 . ~ The same oxidation (m-chloroperbenzoic acid) of the alkene (1) yielded an inseparable mixture of the two possible epoxides (1 1) and (7), in 58% yield and a ratio of 7 : 3. The 13c n.m.r. spectrum was consistent with the structures for (1 1) (6 54 .0 , C 6 ; 57.2, C 7) and (7) (6 51 . 3 , C 6 ; 58.6
Databáze: OpenAIRE
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