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The Synthesis of (+)‐Allopumiliotoxin 323B′
Author(s) -
Tan ChoonHong,
Holmes Andrew B.
Publication year - 2001
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20010504)7:9<1845::aid-chem1845>3.0.co;2-2
Subject(s) - chemistry , intramolecular force , aldehyde , wittig reaction , phosphorane , aldol condensation , cycloaddition , indolizidine , aldol reaction , enone , stereochemistry , protecting group , intramolecular reaction , medicinal chemistry , organic chemistry , catalysis , alkyl , alkaloid
This paper describes the synthesis of (+)‐allopumiliotoxin 323B′ ( 1 ) using the intramolecular [3+2]‐cycloaddition reaction of the ( Z ) ‐N‐ alkenylnitrone 4 . This synthesis began with ( R )‐ tert ‐butyl‐3‐hydroxy‐pent‐4‐enoate [( R ) ‐13 ] which was obtained by enzymatic resolution with Amano PS lipase. A series of manipulations gave intermediate 17 and in situ coupling with 4‐benzoyloxybutanal lead to the ( Z ) ‐N ‐alkenylnitrone 4 which underwent an intramolecular [3+2]‐cycloaddition reaction to give the isoxazolidine 3 as the major cycloadduct. Isoxazolidine 3 provided the piperidinone 24 which upon diastereofacial selective addition of MeMgBr gave the required tertiary alcohol 25 . Formation of the indolizidine core 2 was achieved by an intramolecular S N 2 reaction. The side chain was assembled from a Wittig reaction between the phosphorane 8 and the enantiomerically pure aldehyde 9 . Further modifications afforded the aldehyde 7 which underwent an aldol condensation with the potassium enolate of the indolizidone core 2 . Dehydration gave the enone 37 which was converted into the anti ‐diol 38 by intramolecular hydride reduction. Finally, deprotection of the BOM protecting group gave (+)‐allopumiliotoxin 323B′ ( 1 ).