Premium
Total Synthesis of Silyl‐Protected Early Intermediates of Polyketide Biosynthesis
Author(s) -
Krohn Karsten,
Vidal Anne,
TranThien Hoan Trang,
Flörke Ulrich,
Bechthold Andreas,
Dujardin Gilles,
Green Ivan
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201000067
Subject(s) - chemistry , silylation , polyketide , acetylacetone , ethyl acetoacetate , stereochemistry , silyl ether , biosynthesis , total synthesis , organic chemistry , catalysis , enzyme
The ketal‐ or dithioketal‐protected isocoumarins 15 – 18 gave the corresponding 1‐naphthols 21 – 26 in their reactions with the acetoacetate ( 10 ) or pentane‐2,4‐dione ( 19 ) dianions and the acetone monoanion. Subjection of the dithioketal‐protected ester 28 to Baker–Venkataraman reaction conditions led to the 8‐deoxy tautomeric, protected forms 29 / 30 of the early decaketide antibiotic intermediate 2b . However, the dithioketal protecting groups could not be removed without destruction of the molecule. Consequently the silyl‐protected unstable early tri‐ and tetracyclic decaketide biosynthesis intermediates 37a , 37b , and 38a (precursors of angucycline and anthracycline antitumor antibiotics) were prepared through silylation of 33a and 33b , to afford 34a and 34b , and subsequent treatment with acetylacetone dianion. The ultimate synthetic goal, the silyl‐protected 2,3‐dialkylated naphthol derivative 41 , was achieved by selective elongation of the bottom chain of the bis‐silyl‐protected methyl ester 36 with acetylacetone dianion.