Formal total synthesis of (-)-hamigeran B from a chemo-enzymatically prepared building block with quaternary chiral center
Formal total synthesis of (-)-hamigeran B from a chemo-enzymatically prepared building block with quaternary chiral center
复制标题
DOI：
10.1016/j.tet.2017.12.054
复制
发表时间：
2018-02-15
期刊：
影响因子：
2.1
通讯作者：
Sugai, Takeshi
中科院分区：
文献类型：
--
作者：
Kuwata, Kazuaki;Fujita, Rie;Sugai, Takeshi
从市售的2-氧代环戊烷羧酸乙酯经17步完成了（-）-Hamiglitazone B的正式全合成。羰基还原酶催化的不对称还原和随后的化学转化提供了对映体纯的合成中间体（R）-5-甲酰基-2-异丙基-5-甲基环戊二烯-1-烯-1-基三氟甲基磺酸酯。在PdCl_2（dppf）中心点CH_2Cl_2催化下，Suzuki-Miyaura与Gao的芳基硼酸酯[2-（2-甲酰基-3-甲氧基-5-甲基苯基）-4，4，5，5-四甲基-1，3，2-二氧杂硼杂环戊烷]发生偶联反应，随后通过分子内还原性Sm_2介导的1，2-二醇形成环化反应，得到了一个在C-1和C-9 b之间具有四取代双键的三环骨架。在该双键氢化后，建立了剩余手性中心的适当立体化学。由于C-4醇上的大体积TBS保护基团屏蔽了α-面，因此发生了从β-面的氢原子的排他性加成。氢化产物转化为克莱夫合成的（-）-Hamiglitazone B的前体。(C)2017爱思唯尔有限公司版权所有
A formal total synthesis of (-)-hamigeran B was achieved in 17 steps from commercially available ethyl 2-oxocyclopentanecarboxylate. Carbonyl reductase-catalyzed asymmetric reduction and the subsequent chemical transformations furnished an enantiomerically pure synthetic intermediate, (R)-5-formyl-2-isopropyl-5-methylcyclopent-1-en-1-yl trifluoromethylsulfonate. Suzuki-Miyaura coupling with Gao's arylboronate [2-(2-formyl-3-methoxy-5-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane], under PdCl2(dppf)center dot CH2Cl2 catalysis, and the subsequent cyclization by way of intramolecular reductive SmI2-mediated 1,2-diol formation provided a tricyclic skeleton with a tetrasubstituted double bond between C-1 and C-9b. Upon hydrogenation of this double bond, the proper stereochemistry of the remaining chiral centers was established. Exclusive addition of the hydrogen atom from the beta-face occurred, owing to the shielding of the alpha-face with a bulky TBS protective group on the C-4 alcohol. The hydrogenation products were transformed into Clive's synthetic precursor for (-)-hamigeran B. (C) 2017 Elsevier Ltd. All rights reserved.