Digitoxose as powerful glycosyls for building multifarious glycoconjugates of natural products and un-natural products

Abstract

Digitoxose, a significant 2,6-dideoxyhexose found in nature, exists in many small-molecule natural products. These digitoxose-containing natural products can be divided into steroids, macrolides, macrolactams, anthracyclines, quinones, enediynes, acyclic polyene, indoles and oligosaccharides, that exhibit antibacterial, anti-viral, antiarrhythmic, and antitumor activities respectively. As most of digitoxose-containing natural products for clinical application or preclinical tests, this review also summarizes the biosynthesis of digitoxose, and application of compound diversification by introducing sugar plasmids. It may provide a practical approach to expanding the diversity of digitoxose-containing products.

Keywords: Biosynthesis; Digitoxose; Digitoxose glycosylation; Small-molecule natural products.

Graphical abstract

Fig. 1

Ten types of digitoxose presented in natural products (Ⅰ-ⅩⅠ).

Fig. 2

Structures of digitoxose containing macrolides and macrolactams (1–24).

Fig. 3

Structures of anthracyclines and quinones with digitoxose moiety (25–40).

Fig. 4

Digitoxose containing steroids and their glycosides (41–44) A Structures of compound 41–44. B Relative binding affinities of 43, 44, and their derivatives.

Fig. 5

Structures of digitoxose containing natural products (45–50).

Fig. 6

Biosyntheses of TDP-digitoxose.

Fig. 7

Modification of glycosyl side chain by blocking digitoxose synthetic pathway. A jadomycin B. B lobophorins A and B.

Fig. 8

Engineer glycosylation of bioactive compounds by sugar plasmids encode the biosynthesis of digitoxoses. A Schematic of the formation of digitoxose by plasmids PLNBIV and pMP3*BII. B Chemical structures of MTM and its derivatives. C Chemical structures of steffimycin and its derivatives. D Chemical structures of tetracenomycin and its derivative.