A Total Synthesis of the Styryllactone (+)-Goniodiol from Naphthalene

Abstract

The cytotoxic natural product (+)-goniodiol (1) has been prepared in twelve steps from the enantiomerically pure cis-dihydrocatechol (2), which is readily obtained by microbial oxidation of naphthalene. Elaboration of compound (2) involves an initial oxidative cleavage to dialdehyde (7) followed by reduction to give diol (12). Conversion of compound (12) into acetal (17) required, inter alia, selective oxidation of the benzylic alcohol moiety followed by a metal-catalyzed decarbonylation of the resulting aldehyde. Allylation of compound (17) with allyltributylstannane in the presence of lithium perchlorate gave a ca. 2.7 : 1 mixture of alcohols (18) and (19), each of which was converted into the corresponding acrylate under standard conditions. Subjection of these ester derivatives to a ring-closing metathesis (RCM) reaction with Grubbs' first-generation catalyst gave the anticipated lactones (22) and (23). Acid-catalyzed removal of the acetonide protecting group within compound (22) then afforded (+)-goniodiol (1), while analogous deprotection of congener (23) afforded 6-epi-(+)-goniodiol (24).

The Exploitation of Enzymatically‐Derived cis‐1,2‐Dihydrocatechols and Related Compounds in the Synthesis of Biologically Active Natural Products

“…We have also exploited the sorts of chemical “cutting” (through ozonolysis) and “stitching” (often using RCM) processes described in Schemes and in developing syntheses of a range of other macrolides including (−)‐cladospolides A ( 34 ) and B ( 35 ), the resorcylic acid lactone L‐783,290 ( 36 ), its cis ‐isomer L‐784,277 ( 37 ), ent ‐bengamide E ( 38 ) and goniodiol ( 39 ) …”

A highly enantioselective total synthesis of (+)-goniodiol

“…E-mail: e.tate@ imperial.ac.uk; Fax: +44 20 7594 1139; Tel: +44 20 7594 5720 b Department of Chemistry, The University of Manchester, Manchester, UK M13 9PL. E-mail: Darren.Dixon@man.ac.uk; Fax: +44 161 2754939; Tel: +44 161 2751426 methodologies: generation of oxygenated lactones via furan oxidation; 15 glycoside-templated synthesis; 16-19 chiral induction via enantiopure chromium aryl complexes; 20,21 anomeric oxygen-tocarbon rearrangements; 22 enantioselective enzymatic oxidation of naphthalene derivatives; 23, 24 and ring-closing metathesis. [25][26][27] We have developed a general method for the introduction of carbon linked substituents adjacent to the heteroatom in pyranyl and furanyl ring systems via Lewis acid mediated oxygen-tocarbon rearrangements of a variety of different anomerically linked carbon centred nucleophiles.…”

Total Synthesis of (+)-Viridianol, a Marine-Derived Sesquiterpene Embodying the Decahydrocyclobuta[d]indene Framework

“…The mixture of product esters was saponified, the resulting diols 22 (78% combined yield of a 2:1 mixture of epimers from 20) could be separated chromatographically, and each proved to be crystalline, allowing for single-crystal X-ray analyses of both of them and establishing the illustrated absolute configuration of the compounds in the series (see SI for details). Oxidation of these diols with Dess−Martin periodinane (DMP) gave the corresponding aldehydes, and each of these was immediately subject to decarbonylation using Wilkinson's catalyst [RhCl-(PPh 3 ) 3 ], 19 thus affording target 4 in 40% yield (from 22). All of the IR, MS, 1 H, and 13 C NMR spectral data obtained on compound 4, details of which are presented in Experimental Section, were in complete accord with the assigned structure.…”