Studies toward the enantioselective total synthesis of pectenotoxin 2
Studies toward the enantioselective total synthesis of the marine natural toxin pectenotoxin 2 are described. A successful approach to a fully functionalized precursor to the C(29)-C(40) F/G sector began with the establishment of a proper stereochemical relationship between the hydroxyl and methyl substituents at C(37) and C(38) and involved an anti-aldol reaction. The F ring framework was merged by means of vinyl anion coupling. A new hydroxyl-directed hydrogenation protocol featuring ionic bonding between an alkoxide and rhodium catalyst was invented to arrest the pronounced tendency of hydroxy dihydrofurans to undergo dehydration to form more stable furans. A great level of efficiency was gained by routing the synthesis of the C(16)-C(26) subunit through a common intermediate. The carbon framework was then assembled via a Julia coupling process. The resulting double bond was oxidized by way of a Sharpless asymmetric dihydroxylation reaction to produce two new sterecenters and form the ring E tetrahydrofuranyl system. Access to the C(1)-C(15) building block was achieved by convergent coupling of a lithiated alkane to a Weinreb amide. The spirocyclic A/B motif was next constructed in a synchronous manner by two-fold p-methoxybenzyl ether deprotection. Catalytic á-hydroxylation of a conjugated double bond was called upon to complete the oxygenation pattern of this fragment. Union of the C(1)-C(15) and C(16)-C(26) fragments by means of Julia olefination led to construction of the AB(CD)E eastern hemisphere of pectenotoxin 2. Although the route to this target is far from complete, knowledge collected herein should pave the way toward completion of the total synthesis of this fascinating natural product.
School:The Ohio State University
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:pectenotoxins synthesis hydroxyl directed hydrogenation
Date of Publication:01/01/2005