维生素K的多种合成方法及生物学应用展望

Satyanarayana Battula
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摘要

维生素k是市场上要求很高的多功能保健品,属于一类类异戊二烯分子,由甲基萘醌(MK)单元连接在异戊二烯侧链上。它们是脂溶性的,侧链的程度不同,在自然界中以维生素K1(叶绿醌)、甲基萘醌/维生素K2和其他脂醌的形式获得。由于具有聚戊烯基侧链,它们具有疏水/亲脂性。一般来说,维生素K及其变体的合成受到异构化的影响(例如,确定了顺式/反式MK-7的11种异构体)。自然,在生物系统中,维生素K分别通过莽草酸途径和萜烯生物合成途径产生,用于合成甲基萘醌部分和丙烯基侧链部分。美那酮或其助剂通常被用作通过缩合反应、Friedel-Craft烷基化反应、Claisen重排、Diels-Alder反应等合成维生素K变体的底物。重要的是,有机金属试剂,如格氏,吉尔曼,有机碲化物和其他试剂可能是合成各种维生素K的有前途和一致的底物选择。众所周知,维生素K具有凝血作用。作为一种抗出血维生素,它目前也被用于治疗骨骼和血管疾病。此外,维生素k对于维生素k依赖蛋白(VKD)的激活是必不可少的,几乎存在于所有组织中,负责止血、骨矿化、动脉钙化、细胞凋亡、吞噬、生长控制、趋化和信号转导。本章综述了维生素K及其衍生物的各种合成方法及其生物学功能。
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A Perspective of Diverse Synthetic Approaches and Biological Applications of Vitamin K
Vitamin-K is a demanding multi-functional health product in the market and belongs to a class of isoprenoid molecules that comprises methylnaphthoquinone (MK) unit attached to an isoprene side chain. They are fat soluble and differ in the extent of side chain & obtained in the nature as vitamin K1 (phylloquinone), menaquinone/vitamin K2, and other lipoquinones. Owing to their owned polyprenyl side chain, they are hydrophobic/lipophilic in nature. Generally, the synthesis of vitamin K and its variants suffers with isomerization (for example 11 isomers were identified for cis/trans MK-7). Naturally, in bio-systems vitamin K produces through shikimic acid pathway and terpene biosynthetic pathway for the synthesis of menaquinone part & prenyl side chain parts respectively. Menadione or its auxiliaries are commonly being used as substrates to the synthesis of vitamin K variants through the involvement of condensation reactions, Friedel-Craft alkylation’s, Claisen rearrangement, Diels-Alder reactions and others. Importantly, organometallic reagents, such as Grignard, Gilman, organotelluride and other reagents could be the promising and consistent choice of substrate to the synthesis of various vitamin K’s. Vitamin K is well known for blood coagulation. As an antihaemorrhagic vitamin, it’s also being the current interest for the treatment of bone and vascular diseases. In addition, vitamin k is indispensable for the activation of vitamin K dependent (VKD) proteins and that are present almost in all tissues and responsible for hemostasis, bone mineralization, arterial calcification, apoptosis, phagocytosis, growth control, chemotaxis, and signal transduction. This chapter summarizes various synthetic approaches of vitamin K & derivatives and their biological functions.
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