Total Synthesis of (±)-Allocolchicine and Its Analogues Using Co-Catalyzed Alkyne [2 + 2 + 2]-Cyclotrimerization

Dinesh J Paymode; Chepuri V Ramana

doi:10.1021/acsomega.7b00980

Total Synthesis of (±)-Allocolchicine and Its Analogues Using Co-Catalyzed Alkyne [2 + 2 + 2]-Cyclotrimerization

ACS Omega. 2017 Sep 8;2(9):5591-5600. doi: 10.1021/acsomega.7b00980. eCollection 2017 Sep 30.

Authors

Dinesh J Paymode^{1

2}, Chepuri V Ramana^{1

2}

Affiliations

¹ Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, Maharashtra, India.
² Academy of Scientific and Innovative Research (AcSIR), New Delhi 110020, India.

Abstract

The total synthesis of (±)-allocolchicine has been completed by employing cobalt-catalyzed alkyne [2 + 2 + 2]-cyclotrimerization as the key reaction. The essential diyne has been synthesized from easily available 3,4,5-trimethoxybenzaldehyde following simple chemical transformations. In general, the cycloaddition gave a mixture of C(9) and C(10) isomers thus allowing the synthesis of both allocolchicine and its C(10)-carboxylate. Because this cycloaddition was employed at the penultimate stage, it allowed the synthesis of various analogues having the diverse functionality at C(9) and/or C(10) of ring C.