Unified stereochemical model of polyether antibiotic structure and biogenesis

Abstract

3594bromo silyl ether 1Sb): 11-cis-loa (23.4 mg, 5.4%), 1 l-cis,l3-cis-l2a J . Am. Chem. SOC. 1983, 105, 3594-3600 Grant EY-02452 and NCI Contract CP-05715) Drovided financial (43.4 mg; lo%), IS%), and 9-cis,llcis-lla (29.6 mg, 6.8%).12,20-Tetramethyleneretinals lob, 1 lb, 12b, and 13b. General Procedure. The seven-membered ring 12,20-tetramethyIeneretinals were prepared by MnOz oxidation of the corresponding retinols according to the procedure described for the six-membered-ring 12,20-trimethyleneretinals 7b. Sb. and 9b. The four seven-membered-ring isomers 1 l-cis-support for this project. ) for 500-MHz spectra, and BASF (Ludwigshafen) for chemicals. Finally, we remain most grateful to Professor R o b e r t R. Birge of this delob, 9-cis,i l-cis-llb, l l-cis,l3-cis-l2b, and 9-cis.1 l-cii13-cis-13b were partment for informative discussions. prepared in yields ranging from 50 to 80%.Preparation of Cyclized Product 29: Thermolyses of 12,20-Tetramethylene-9-cis,ll-cis-retinol ( l l a ) and -9-cis,ll-cis,l3-cis-retinol (13s). The 9-cis,ll-cis-isomer l l a (-2 mg) in freshly distilled hexanes (10 mL) was added under argon to a refluxing solution of hexanes (100 mL). Aliquots were removed at various time intervals and analyzed by high-pressure LC (Waters p-porasil column, 15% ethyl acetate/skellysolve B). Essentially quantitative conversion of the retinol l l a to the cyclized product 29 was complete in -3 h. By contrast, the 9-cis,ll-Registry No.

Nature as organic chemist

“…45,46 On the basis of these latter discoveries, we extended an original suggestion of Dr John Westley of Hoffman-La Roche for the biosynthesis of lasalocids and proposed a general stereochemical model of polyether biosynthesis, involving the nucleophilic cascade cyclization of polyepoxide intermediates derived from an initially formed all-E-unsaturated polyketide ( Figure 9). 47 In recent years, this biosynthetic hypothesis has been strongly validated by an array of independent molecular genetic, biochemical, and structural biological studies by Prof Peter Leadlay 48,49 at the University of Cambridge and Prof Hideaki Oikawa 50,51 at the University of Hokkaido.…”

On the Origin of Siphonariid Polypropionates: Total Synthesis of Caloundrin B and Its Isomerization to Siphonarin B

“…16 The studies revealed that these metabolites arose from condensation of propionate-derived units similar to the biosynthesis of macrolide 17 and polyether antibiotics. 18 Some years later,…”

“…After stirring at 40 °C for 1 day, the mixture was diluted with ethyl acetate, washed sequentially with 1% aq citric acid (x3), saturated aq NaHCO 3 and brine, dried over Na 2 SO 4 , concentrated, and fractionated by FCC (5% diethyl ether in hexanes) to yield the titled compound (62 mg, 14%; dr [16][17][18] and recovered ent-10-epi-167 (338 mg, 80%; dr [16][17][18]. The latter fraction was re-subjected to the isomerization conditions and after a total of six isomerization cycles, recovered ent-10-epi-167 (119 mg, 28%; dr [16][17][18] (q, CH 3 C-8'), 12.7 (q, CH 3 C-10'), 7.9 (q, CH 3 C-9'), 7.5 (q, C-3), 6.4 (q, CH 3 CC-3'), 2.2 (q ×3, 29.6 (t, CH 2 C-3'), 27.4 (t, C-4), 13.5 (q, CH 3 C-8'), 12.6 (q, CH 3 C-10'), 10.7 (q, C-5), 7.9 (q, CH 3 C-9'), 6.5 (q, CH 3 CC-3'), 4.5 (q, C-1), 2.2 (q ×3, CH 3 …”

Characterization of an Epoxide Hydrolase from the Florida Red Tide Dinoflagellate, Karenia brevis

“…As described previously, EHs are believed to be able to cyclize polyepoxides into polyethers 55 . EHs from Karenia brevis were proposed to catalyze a kinetically disfavored endo-tet cyclization to produce brevetoxins from polyene precursors.…”