Ahmad Sajjad, Akhtar Rabia, Zahoor Ameer Fawad
Department of Chemistry, University of Engineering and Technology Lahore, Faisalabad Campus, 38000-Faisalabad, Pakistan.
Department of Chemistry, Government College University, 38000, Faisalabad, Pakistan.
Curr Org Synth. 2022;19(1):56-85. doi: 10.2174/1570179418666210809131917.
A variety of diseases have been associated with hyperactivation of protein kinase C (PKC) enzymes such as cancer, diabetes, asthma, cardiovascular and central nervous system disorders. There is a dire need to selectively inhibit these enzymes by synthesizing new potent inhibitors. Balanol, a fungal metabolite belonging to the PKC inhibitor family, is especially included in this aspect. Tremendous effort has been put towards the synthesis of balanol by different research groups.
The aim of this review is to provide a detailed description of synthetic approaches adopted for the synthesis of key fragments of balanol (azepane and benzophenone). All the factors that resulted in excellent yield and high enantioselectivity have also been mentioned.
It has been shown throughout this review that the synthesis of hexahydroazepine and benzophenone cores of balanol was achieved by employing a variety of important key steps with commercially available starting precursors, which make this total synthesis more valuable. Moreover, this article provides ideas to the synthetic as well as pharmaceutical chemists for the synthesis of (-)-balanol and its analogues.
多种疾病与蛋白激酶C（PKC）酶的过度激活有关，如癌症、糖尿病、哮喘、心血管疾病和中枢神经系统疾病。迫切需要通过合成新的强效抑制剂来选择性抑制这些酶。巴拉诺醇是一种属于PKC抑制剂家族的真菌代谢产物，尤其涉及这一方面。不同研究小组在巴拉诺醇的合成方面付出了巨大努力。
本综述的目的是详细描述用于合成巴拉诺醇关键片段（氮杂环庚烷和二苯甲酮）的合成方法。还提到了所有导致高产率和高对映选择性的因素。
本综述表明，通过使用各种重要的关键步骤以及市售起始前体，实现了巴拉诺醇六氢氮杂环庚烷和二苯甲酮核心的合成，这使得该全合成更具价值。此外，本文为合成化学家以及药物化学家合成（-）-巴拉诺醇及其类似物提供了思路。
