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Stereoselective Synthesis of the C(1)−C(12) Fragments of Tedanolides − Application of a syn ‐Selective Tin(II)‐Mediated Aldol Reaction and a Convertible Methoxybenzyl Protecting Group
Author(s) -
Matsui Katsuya,
Zheng BaoZhong,
Kusaka Shinichi,
Kuroda Masaya,
Yoshimoto Katsuya,
Yamada Haruo,
Yonemitsu Osamu
Publication year - 2001
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 - 10.1002/1099-0690(200110)2001:19<3615::aid-ejoc3615>3.0.co;2-p
Subject(s) - chemistry , aldol reaction , stereoselectivity , protecting group , aldehyde , stereochemistry , amide , ketone , moiety , diol , tin , acetal , medicinal chemistry , organic chemistry , catalysis , alkyl
Stereoselective synthesis of two C(1)−C(12) fragments, 3 and 4 , of antitumor agents tedanolide ( 1 ) and 13‐deoxytedanolide ( 2 ) was achieved by means of several regio‐ and/or stereoselective reactions. Ethyl ketone 14 was synthesized from methyl ( S )‐3‐hydroxy‐2‐methylpropionate ( 16a ) by way of a Weinreb amide. A highly syn ‐selective tin(II)‐mediated aldol reaction between 14 and aldehyde 15 , prepared from ( R )‐propionate 16b, proceeded smoothly, and subsequent reduction gave diol 13 , which was transformed into 3 , incorporating a C(3),C(5)‐MP acetal moiety, by taking advantage of convertible MPM protecting groups. Another fragment, 4 , with C(3)‐ O ‐methyl and C(5)‐ O ‐MPM groups, was also synthesized. A crucial step was the selective transformation of C(2),C(3)‐diol 21 into C(2)‐ O ‐TBS, C(3)‐ O ‐Me compound 22 .