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Synthesis of a Glyoxalase I Inhibitor from Streptomyces griseosporeus N IIDA et O GASAWARA
Author(s) -
Mirza Sohail,
Molleyres LouisPierre,
Vasella Andrea
Publication year - 1985
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19850680425
Subject(s) - chemistry , yield (engineering) , formaldehyde , stereochemistry , steric effects , streptomyces , medicinal chemistry , organic chemistry , bacteria , genetics , materials science , biology , metallurgy
The pseudolactones 6 and 12 were prepared in a straightforward way from methyl α‐ D ‐glucopyranoside and methyl α‐ D ‐mannopyranoside, respectively. The pseudolactone 6 reacted with tert ‐butyl lithioacetate to give the protected, trihydroxylated cyclohexenone carboxylate 7 (51 %). The sterically hindered, L‐ ribo ‐configurated pseudolactone 12 reacted with diethyl ethylphosphonate and dimethyl methylphosphonate to give the protected trihydroxycyclohexenones 17 (49 %) and 18 (62 %), respectively. The hydroxymethylated cyclohexenone 21 was obtained from 18 by treatment with Me 2 AlSPh and then formaldehyde, oxidation of the product 19 , and elimination. Deprotection of 21 gave 2 , identical with KD16‐Ul. Esterification of 2 gave 1 , identical with the title compound. Alternatively, 1 was obtained in higher yields by esterification of 21 , followed by deprotection of the hydroxy groups. This synthesis gave 1 and 2 from methyl α‐ D ‐mannopyranoside in an overall yield of 18 and 20 %, respectively, confirming their absolute configuration.