Font Size: a A A

A second-generation total synthesis of leucascandrolide A: A Mukaiyama aldol-Prins approach, and, Progress towards a reagent-controlled, stereoselective synthesis of 2,5-cis and 2,5-trans substituted tetrahydrofuran rings

Posted on:2008-01-30Degree:Ph.DType:Thesis
University:University of California, IrvineCandidate:Van Orden, Lori JeanFull Text:PDF
GTID:2441390005454516Subject:Chemistry
Abstract/Summary:
A second-generation total synthesis of the highly cytotoxic and fungistatic marine natural product leucascandrolide A was completed using a convergent and efficient strategy. The titanium tetrabromide-mediated Mukaiyama aldol-Prins (MAP) reaction of an aldehyde and enol ether was used to assemble the core of the molecule in high yield and selectivity. The total synthesis was completed by coupling of the side chain through two avenues: a known Still-Gennari olefination and a new Z-selective aldol/dehydroselenation reaction. Both procedures were highly selective and provided the natural product.; The authenticity of synthetic leucascandrolide A and many of its intermediates were confirmed by analysis of the spectroscopic data, which were consistent with those of previous syntheses.; Structural characteristics of leucascandrolide A led to an investigation into the first MAP reactions with acetals as coupling partners. Based on the results of these studies, mechanistic rationales that may explain the origins of diastereoselectivity for MAP reactions with either type of coupling partner were proposed.; A process for the diastereoselective cyclization of bis(homoallylic) alcohols in the formation of 2,5-cis and 2,5-trans tetrahydrofuran rings was investigated. Both a palladium (II) catalyst and a cobalt (III) catalyst, which were precedented for similar processes, were explored.
Keywords/Search Tags:Total synthesis, Leucascandrolide
Related items
1 I. The total synthesis of leucascandrolide A. II. Studies directed toward the total synthesis of ingenol
2 Total synthesis of leucascandrolide A and apicularen A and synthesis of natural product-like macrodiolides
3 Studies directed toward the total synthesis of leucascandrolide A, and, Catalytic asymmetric carbenoid insertions into the silicon-hydrogen bond catalyzed by chiral copper-(I) Schiff base complexes
4 The development of novel electron transfer initiated cyclization (ETIC) reactions: Discovery of the diastereoselective ETIC reaction and its application toward the total synthesis of leucascandrolide A
5 The application of asymmetric catalysis to the synthesis of natural products: A total synthesis of (-)-tubulosine, progress towards a total synthesis of (+)-reserpine, and a total synthesis of (+)-peloruside A
6 New methods and strategies for heterocycle synthesis: Progress toward the total synthesis of upenamide and the total synthesis of (+)-5-epiindolizidine 167B and indolizidine 223AB
7 Total synthesis of ht-13-A and ht-13-B, total synthesis of aurantioclavine, progress towards the synthesis of cycloclavine
8 Enantiospecific stereospecific total synthesis of the oxindole alkaloid (+)-alstonisine and stereocontrolled total synthesis of (-)-11-methoxy-17-epivincamajine as well as studies directed toward the total synthesis of N(b)-demethylalstophylline oxindole
9 Part I: The first regio- and atropdiastereoselective total synthesis of the dimeric indole alkaloid (+)-dispegatrine, as well as the first total synthesis of the sarpagine alkaloids (+)-spegatrine, lochvinerine, (+)-lochneram and an improved total synthes
10 Total Syntheses Of (+)-Agelastatin A And B, Longifolene And (+)-Minfiensine, And Studies Toward Total Synthesis Of Daphniyunnine C