Bajorath Jürgen
Albany Molecular Research, Inc., Bothell Research Center, 18804 North Creek Pkwy, Bothell, Washington 98011, USA.
J Comput Aided Mol Des. 2002 May-Jun;16(5-6):431-9. doi: 10.1023/a:1020868022748.
Until recently, the field of diversity and library design has more or less ignored natural products as a compound source. This is probably due to at least two reasons. First, combinatorial and reaction-based approaches have been major focal points in the early days of computational library design. In addition, a widespread view is that natural products are often highly complex and not amenable to medicinal chemistry efforts. This contribution introduces recent computational approaches to systematically analyze natural molecules and bridge the gap between natural products and synthetic chemistry programs. Large scale comparisons of natural and synthetic molecules are discussed as well as studies designed to identify 'synthetic mimics' of natural products with specific activity. In addition, a concept for the design of natural/synthetic hybrid libraries is introduced. Although research in this area is still in its early stages, an important lesson to be learned from computational analyses is that there is no need to a priori 'shy away' from natural products as a source for molecular design.
直到最近，多样性与文库设计领域或多或少地忽视了天然产物作为化合物来源。这可能至少有两个原因。首先，在计算文库设计的早期，基于组合和反应的方法一直是主要焦点。此外，一种普遍的观点是，天然产物通常高度复杂，不适合进行药物化学研究。本文介绍了最近用于系统分析天然分子并弥合天然产物与合成化学项目之间差距的计算方法。讨论了天然分子与合成分子的大规模比较以及旨在鉴定具有特定活性的天然产物“合成模拟物”的研究。此外，还介绍了天然/合成混合文库的设计概念。尽管该领域的研究仍处于早期阶段，但从计算分析中学到的一个重要教训是，没有必要先验地“回避”将天然产物作为分子设计的来源。
