Fine Synthetic Nucleoside Chemistry Based on Nucleoside Natural Products Synthesis

Abstract

Synthetic nucleoside chemistry based on nucleoside natural products synthesis were described. First, a samarium diiodide (SmI 2 )-promoted aldol reaction with the use of a a-phenylthioketone as an enolate was developed. The characteristics of this reaction are that the enolate can be regioselectively generated and the aldol reaction proceeds under near neutral condition. This reaction is proved to be a powerful reaction for the synthesis of complex nucleoside natural products, and herbicidin B and fully protected tunicaminyluracil, which were undecose nucleoside natural products, were synthesized. Next, the synthetic methodology of the caprazamycins, which are promising antibacterial nucleoside natural products, was also developed by the strategy including b bselective ribosylation without using a neighboring group participation. Our synthetic route provided a range of key analogues with partial structures to define the pharmacophore. Simplification of the caprazamycins was further pursued to develop diketopiperazine analogs.

Antimicrobial nucleoside antibiotics targeting cell wall assembly: Recent advances in structure–function studies and nucleoside biosynthesis

“…59,60 Ichikawa and Matsuda have reported the synthesis of CPZ-type compounds, and have clarified structure-activity relationships as reviewed below. 61 Kaysser and Gust have identified the CPZ biosynthetic gene cluster, and have proposed a biosynthesis of these compounds as discussed in Section 6.4. Through their studies they have produced nonglycosylated bioactive CPZ derivatives by heterologously expressing the biosynthetic cluster in Streptomyces coelicolor.…”

“…But the deacyl pharmacophore such as deacyl LPM (the same as caprazene), caprazol, or muraminocin Z decreased their biological activities, therefore, the presence of an acyl moiety is crucial for activity. 4,60,61 Comparing the activity of LPMs and CPZs, there is no clear difference in activity with or without a permethylated L-rhamnose.…”

“…Recently, the absolute stereochemistry of caprazole, (the core structure of CPZ) was determined by X-ray crystal structure analysis, and caprazole itself was synthesized. 58,61,77,78 Using synthetic caprazole, Hirano et al have synthesized several truncated analogues and evaluated their antibacterial activity (see Fig. 10).…”

Caprazamycins: Promising lead structures acting on a novel antibacterial target MraY

“…MraY-targeting caprazamycins are therefore speculated to become promising, novel, antibacterial leads effective against drug-resistant bacterial pathogens. Several review articles have enriched the knowledgebase recently, focussing on isolation, biosynthesis, chemical synthesis, modelling and biological activity of nucleoside antibiotics [7,10,[14][15][16][17][18][19][20][21][22][23][24]. Herein, we highlight the structure and function of naturally occurring caprazamycin and discuss its synthetic derivatives' competencies as broad-spectrum antibacterial agents.…”

Efficient and Convenient Palladium‐Catalyzed Amination of Allylic Alcohols with N‐Heterocycles

“…It is well-known that several uridine-containing Nheterocyclic natural products possess antitumor, antiviral, and antifungal properties. [16,17] Selected examples of such compounds are the thymidine analogue AZT, which is used for the treatment of AIDS; [16a] Eniluracil, [16b] which is widely used as anticancer drug; Capuramycin; [16c] [16d] and Caprazol. [16d] Moreover, uridine and its analogues are used for the synthesis of complex nucleoside antibiotics for drug development.…”