天然产物药物开发中资源问题的解决方案概述

The solutions for supply problems in development of natural product-derived drugs

天然产物是现代药物开发中先导结构的重要来源,但是天然活性先导化合物在天然生命体中往往含量微少,这严重限制了其临床前及临床研究,难以满足其后续的市场需求。本文通过具体案例剖析,归纳总结了源于结构复杂的天然产物在药物开发中资源问题的几种有效解决方案:1寻找量丰的核心天然骨架,再经半合成制备;2寻找其量丰的生源合成前体经仿生合成制备;3由量丰天然类似物经化学转化制备;4简化先导结构再全合成制备。希望为解决复杂天然产物药物开发中的资源供应提供借鉴。

Natural products play a vital role in drug development as an important source of lead compounds.However,the amounts of biological active natural compounds,especially the complex entities,are usually deficient in nature for preclinical and clinical research.The problem of supply further restricts the development of the natural active products into market. This article briefly concluded four solutions for the problem of supply in order to provide experience for natural product-derived drugs development： 1semi-synthesis from the abundant skeletons; 2biomimetic synthesis from plentiful biosynthetic precursors; 3chemical transformation from rich natural analogues; 4full-synthesis after simplifying lead compounds.