Insights into the biosynthesis of septacidin L-heptosamine moiety unveils a VOC family sugar epimerase

L-Heptopyranoses are important components of bacterial polysaccharides and biological active secondary metabolites like septacidin(SEP),which represents a group of nucleoside antibiotics with antitumor,antifungal,and pain-relief activities.However,little is known about the formation mechanisms of those L-heptose moieties.In this study,we deciphered the biosynthetic pathway of the L,L-gluco-heptosamine moiety in SEPs by functional characterizing four genes and proposed that SepI initiates the process by oxidizing the 4’-hydroxyl of L-glycero-α-D-manno-heptose moiety of SEP-328(2)to a keto group.Subsequently,SepJ(C5 epimerase)and SepA(C3 epimerase)shape the 4’-keto-L-heptopyranose moiety by sequential epimerization reactions.At the last step,an aminotransferase SepG installs the 4’-amino group of the L,L-gluco-heptosamine moiety to generate SEP-327(3).An interesting phenomenon is that the SEP intermediates with 4’-keto-L-heptopyranose moieties exist as special bicyclic sugars with hemiacetal-hemiketal structures.Notably,L-pyranose is usually converted from D-pyranose by bifunctional C3/C5 epimerase.SepA is an unprecedented monofunctional L-pyranose C3 epimerase.Further in silico and experimental studies revealed that it represents an overlooked metal dependent-sugar epimerase family bearing vicinal oxygen chelate(VOC)architecture.

Synthesis and in vino Antimalarial Activity of Several Simple Analogues of Peroxyplakoric Acid

Several simple analogues of peroxyplakoric acid were synthesized by using Kobayashi＇s method to construct the key 1,2-dioxane core and tested in vitro for antimalarial activity. The scope and limitation of the method was also briefly examined.

Synthesis of a Nitro Analogue of Plakoric Acid

Synthesis of a nitro analogue of plakoric acid is presented. The peroxy bond was incorporated into the substrate structure through a boron trifluoride etherate catalyzed methoxy-hydroperoxy group partial exchange reaction in diethyl ether with urea-hydrogen peroxide complex （UHP, a commercially available solid reagent） as the source of the hydrogen peroxide. Under the given conditions, only one of the two methoxyl groups underwent the MeO—— OOH exchange and the resulting hydroperoxy hemiketal proceeded directly to the end product through an intramolecular Michael addition of the hydroperoxyl group to the nitro group activated carbon-carbon double bond.

Synthesis of 1,2-Dioxane Type Antimalarial Peroxides

Synthesis of five simple analogues of peroxyplakoric acid by using Kobayashi＇s method to construct the key 1,2-dioxane core is detailed.