Enantioselective Total Synthesis of (+)-Neosymbioimine

Abstract

[reaction: see text] The enantioselective total synthesis of (+)-neosymbioimine was accomplished in 18 steps from (-)-(S)-citronellol utilizing an organocatalytic alpha-oxidation of aldehyde 6. The carbon core was constructed by a tandem Horner-Wadsworth-Emmons (HWE) reaction and an intramolecular Diels-Alder cyclization. All double bonds of 12 were made in a stereoselective manner by Wittig-type reactions. Selective formation of the monosulfate monoester was accomplished by one-pot excessive sulfation followed by kinetic hydrolysis of bissulfate 18 in 79% yield.

Marine natural products

“…236 The enantioselective total synthesis of (+)-neosymbioimine, an iminium metabolite from the dinoflagellate Symbiodinium sp., 237 from (À)-(S)-citronellol established the absolute configuration as 208. 238 A culture of Aspergillus versicolor (Petrosia sp., Jeju Is., Korea) yielded three known polyketides, decumbenones A, B 239 and versiol, 240 and was the first isolation of these compounds from a marine source. 241 Three known compounds, 3-methoxyphenol, 242 4-methoxyphenylacetic acid 243 and 4-hydroxy-2-methoxyacetanilide, 244 all inhibitors of cytochrome P450, were isolated from the marine environment for the first time from a culture of a Penicillium sp.…”

Synthesis of Spongidepsin and Analogs

“…The construction of the C6-C13 fragment started with the commercially available (-)-citronellol which, after protection of the primary hydroxy group and ozonolysis provided aldehyde 38 in 86 % yield. The key stereoselective step was then the introduction of the hydroxy group at C9 according to McMillan α-hydroxylation [32][33][34][35][36] of aldehyde 38 using nitrosobenzene and D-proline (40 mol-%) in DMSO followed by a NaBH 4 reduction. The resulting anilinoxy derivative was then treated with CuSO 4 (30 mol-%, MeOH) to cleave the N-O bond and diol 39 was isolated in 53 % yield with an excellent diastereoselectivity (de = 98 %).…”

Applications of the Wittig Reaction on the Synthesis of Natural and Natural‐Analogue Heterocyclic Compounds

“…One of the developed synthetic routes for neosymbioimine 19 , a (±)‐symbioimine analogue isolated in 2005, called our attention due to its recurrent use of the Wittig or Wittig‐type reactions . The methodology involves 18 steps and the neosymbioimine 19 was obtained in an overall yield of 10 % (Scheme ).…”