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(+)‐11,11′‐Di‐ O ‐methylelaiophylidene – preparation from elaiophylin and total synthesis from ( R )‐3‐hydroxybutyrate and ( S )‐malate
Author(s) -
Seebach Dieter,
Chow HakFun,
Jackson Richard F. W.,
Sutter Marius A.,
Thaisrivongs Suvit,
Zimmermann Jürg
Publication year - 1986
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.198619860714
Subject(s) - chemistry , stereocenter , aldol reaction , stereochemistry , ketone , malic acid , diastereomer , aglycone , lactone , enantioselective synthesis , organic chemistry , catalysis , glycoside , citric acid
The macrodiolide antibiotic elaiophylin ( 6 , Scheme 1) is converted into an aglycone 8a by acid‐catalysed cleavage of the deoxyfucoses in methanol, with replacement of two lactol OH‐groups by OCH 3 (C‐11 and C‐11′). The di‐ O ‐methylelaiophylidene ( 8a ), a C 2 ‐symmetrical macrodiolide with 2 × 11 stereogenic units, was synthesised from ( R )‐3‐hydroxy‐butanoate (from the biopolymer PHB) and ( S )‐malic ester, using diastereoselective steps for the generation of the other stereogenic units. The key intermediates (Scheme 2) are the macrocyclic dialdehyde 10 (cf. 26 , 27 ; 2 × 5 stereogenic units) and the silyl‐protected dihydroxy ketone derivative 11 (cf. 34, 35 ; 3 stereogenic units). These two intermediates almost statistically were subjected to aldol coupling with relative topicity ul , using the Z ‐boron enolate of the ketone, to give the two C 2 ‐symmetrical and the asymmetric aldol ( 40a, b, c ), one of which furnished the aglycone 8a upon acid‐catalysed methanolysis (Fig. 1 and 2, NMR spectra). The diastereoselective key steps, by which three of the six new asymmetric carbon atoms are created, are α‐alkylations of β‐hydroxy ester or lactone alkoxide‐enolates (malic acid → 12 and 15 → 16 in the dialdehyde synthesis, hydroxybutanoic acid → 29 in the ketone preparation).