Phospholipids are unique and versatile molecules, essential in a variety of biological systems. Moreover, their diverse structures and amphiphilic properties endorse their indispensable and unparalleled roles in research and industrial-related applications. However, in most cases of applications, naturally occurring phospholipids are either deficit in structural variety or insufficient in quantity; therefore, novel methods must be developed for the synthesis of new molecules or modification of natural structures. To identify sustainable and environmentally friendly approaches, this work reviews the latest progress in the acquisition of structurally defined phospholipids (designer phospholipids) from natural resources, including structural retrieval, redesign and synthesis of designer phospholipids via chemo−/enzymatic approaches. This review additionally highlights the opportunity to use biological systems to direct the production of specific phospholipid species through genetic engineering via defined metabolic pathways, and functionalization of natural phospholipids through synthetic modifications: substitutions, removals or additions of specific functional groups. A particular focus is given to the establishment of chemical and biological systems for the synthesis of isotopically labelled phospholipids for biomedical applications. The application of green chemistry principles in semi-synthesis of phospholipids including extended use of greener biocatalysts and diatomaceous earth and reduced use of hazardous and toxic solvents is also summarized.

磷脂是独特且用途广泛的分子，在各种生物系统中必不可少。此外，它们多样化的结构和两亲性特性证明了它们在研究和工业相关应用中不可或缺且无与伦比的作用。然而，在大多数应用情况下，天然存在的磷脂要么结构多样性不足，要么数量不足；因此，必须开发新的方法来合成新分子或修饰天然结构。为了确定可持续和环境友好的方法，这项工作回顾了从自然资源中获取结构定义的磷脂（设计磷脂）的最新进展，包括通过化学/酶促方法进行结构修复、重新设计和合成设计磷脂。该综述还强调了利用生物系统通过特定代谢途径通过基因工程指导特定磷脂种类的生产，以及通过合成修饰对天然磷脂进行功能化：替代、去除或添加特定官能团的机会。特别关注建立化学和生物系统以合成用于生物医学应用的同位素标记的磷脂。还总结了绿色化学原理在磷脂半合成中的应用，包括延长使用更环保的生物催化剂和硅藻土以及减少使用有害和有毒溶剂。