A Unified Strategy To Construct the Tetracyclic Ring of Calyciphylline A Alkaloids: Total Synthesis of Himalensine A

Abstract

The synthetic approach to the core framework of the calyciphylline A-type Daphniphyllum alkaloids and total synthesis of himalensine A were described herein. Nitrone-induced 1,3-dipolar [3 + 2] cycloaddition was applied for the construction of A/C rings along with the all-carbon quaternary center. Pd-catalyzed enolate alkenylation and ring closing metathesis (RCM) were adopted to install the B/D rings to accomplish the [6,6,5,7] core framework. Nazarov reaction was utilized to install the F ring to complete the total synthesis of himalensine A.

Recent progress in the total synthesis of calyciphylline A-type <italic>Daphniphyllum</italic> alkaloid himalensine A

“…他们从二噻烷和 溴代物出发, 经过5步反应得到不饱和酯61. 接着通过 图 7 徐晶课题组 [28] 对于(−)-himalensine A的全合成 Figure 7 Total synthesis of (−)-himalensine A by the Xu group [28] 图 8 高栓虎课题组 [37] 对于(±)-himalensine A的全合成 Figure 8 Total synthesis of (±)-himalensine A by the Gao group [37] The evergreen plants of the genus Daphniphyllum are found mainly in the Asia-Pacific region and have played important roles in Traditional Chinese Medicine. Their leaves, barks and fruits have long been used to treat a variety of ailments including asthma, rheumatism, inflammation and fever.…”

“…、Fukuyama/Yo-koshima课题组 [17] 、翟宏斌课题组 [18] 和邱发洋课题 组 [19] 等先后报道了多个含相邻双季碳及含苯环结构的 Dixon课题组 [36] 和高栓虎课题组 [37] 也先后漂亮地完成 了himalensine A的全合成工作. 此外, Bonjoch课题 组 [38,39] 、Stockdill课题组 [40] 、Hudlicky课题组 [41] 等也 先后开展了一系列适用于himalensine A全合成的关键 骨架构筑探索.…”

Synthesis of Azabicyclic Building Blocks for Daphniphyllum Alkaloid Intermediates Featuring N‐Trichloroacetyl Enamide 5‐endo‐trig Radical Cyclizations

“…The structural complexity and biological activities of calyciphylline A‐type alkaloids, which comprise a subfamily of Daphniphyllum alkaloids of around fifty members, have attracted the interest of synthetic researchers in the last sesquidecade. However, the only total syntheses achieved to date are of daphenylline, himalensine A, and longeracinphyllin A, all reported recently ( Figure ).…”

A General Strategy for the Construction of Calyciphylline A‐Type Alkaloids: Divergent Total Syntheses of (−)‐Daphenylline and (−)‐Himalensine A

“…[3] Since then, significant efforts toward the syntheses of Daphniphyllum alkaloids have been reported by over twenty groups. The total syntheses of Daphniphyllum family were achieved recently by Carreira, [4] Li, [5] Smith, [6] Fukuyama, [7] Hanessian, [8] Zhai, [9] Dixon, [10] Xu, [11] Gao, [12] Sarpong, [13] Li, [14] and our group. [15] Despite these impressive developments, more efficient and general strategies for assembling calyciphylline A-type alkaloids are still in demand to accelerate their syntheses and biological investigations.…”