Discovery, development and syntheses of tetracycline antibiotics: derivation from natural products and application for human health

Abstract

<p indent="0mm">Tetracycline antibiotics, a class of broad-spectrum antibiotics, are widely used in the treatment of diseases caused by gram-positive and gram-negative bacteria, mycoplasma, chlamydia and rickettsia infections. Tetracycline antibiotics consist of four fused six-membered cycles, <italic>i.e.</italic>, ABCD tetracyclic system. To date, people mainly obtain tetracycline natural antibiotics through fermentation, and then carry out structural modification through chemical semi-synthesis. Among them, the substitution in ring A is found invariable while the modification in ring D is worth exploring so as to obtain new non-natural tetracycline antibiotic drugs with better clinical efficacy. Since Woodward <italic>et al</italic>. completed the total synthesis of tetracycline in 1962, synthetic communities have accomplished several tetracycline antibiotic drugs. In 2005, Myers <italic>et al</italic>. achieved the total synthesis of tetracycline antibiotic drug Doxycycline <italic>via</italic> novel synthetic strategies. Then the total synthesis and structural modifications of other tetracycline antibiotics were efficiently fulfilled which accelerated the development and marketing of new tetracycline antibiotics. In this review article, the discovery and developing history of tetracycline drugs is summarized, and their biosynthetic mechanism and drug action mode against pathogenic bacteria is described, besides the semi-synthetic and total synthesis of various tetracycline drugs, which will play an instructive role for researchers to understand the discovery, development and synthetic scope of tetracycline antibiotics and structurally similar drugs.