The stereochemistry of the Nozaki-Hiyama-Kishi reaction and the construction of 10-membered lactones. The enantioselective total synthesis of (-)-decarestrictine D

Abstract

O uso da reação de Nozaki-Hiyama-Kishi para a formação de lactonas de 10 membros é descrita. A influência dos grupos de proteção em C4 e C5 sobre a estereoquímica do novo centro estereogênico formado em C7 foi investigada. A utilidade desta metodologia ficou demonstrada com a síntese total e estereosseletiva da (-)-decarestrictina D a partir do 1,3-propanodiol e poliidroxibutirato (PHB) em 13 etapas e 6,3% de rendimento total. The use of the intramolecular Nozaki-Hiyama-Kishi reaction to construct 10-membered lactones is described. The influence of the nature of the protecting groups at C4 and C5 on the stereochemistry of the newly formed stereogenic center at C7 was investigated. The utility of this methodology has been demonstrated in the stereoselective total synthesis of (-)-decarestrictine D from 1,3-propanediol and polyhydroxybutyrate (PHB) in 13 steps and 6.3% overall yield.

Stereoselective Synthesis of Decarestrictine D from a Previously Inaccessible (2Z,4E)-Alkadienyl Alcohol Precursor

“…Deprotection of the MOM group of 25 , the last step, was attempted under the conditions using CF 3 CO 2 H/CH 2 Cl 2 , Dowex-50/MeOH, BF 3 ·OEt 2 , and (CH 2 SH) 2 /CH 2 Cl 2 to provide a mixture of products, whereas PPTS in refluxing n -BuOH was found to produce decarestrictine D ( 1 ) cleanly in 81% yield. The 1 H and 13 C NMR spectra of 1 measured in CDCl 3 and in CD 3 OD were identical with those reported. 1c,, In addition, the specific rotation ([α] 24 D −68 ( c 0.066, MeOH)) and mp (121−123 °C, recrystallized from CH 2 Cl 2 /hexane) were also in good agreement with the reported data: [α] 20 D −62 ( c 1.0);1a 118−120 °C (synthetic); 116 °C (natural) 1b…”

“…Taking together its strong and selective biological profile, 1 is an attractive compound for developing a new cholesterol-lowering drug. So far, the synthesis of 1 and the seco acid has been reported by three groups. − However, the syntheses suffer from the low 1,3-chiral induction at C(7) by the C(9) alkoxyl group in the construction of the central core structure by Andrus 2 and Chapleur 4 and excess use of the toxic Cr reagent twice in Pilli's synthesis . In addition, the macrolactonization and macrocyclization at C(7)−C(8) have been accomplished with rather low yields of <33%.…”

Métodos de preparação de lactonas de anel médio

“…Pilli et al 57,58 aplicaram esta metodologia na síntese total da (-)-decarestrictina D (Esquema 25).…”