Necrotizing enterocolitis (NEC) is one of the most common and devastating intestinal disorders in preterm infants. Therapies to meet the clinical needs for this special and highly vulnerable population are extremely limited. A specific human milk oligosaccharide (HMO), disialyllacto-N-tetraose (DSLNT), was shown to contribute to the beneficial effects of breastfeeding as it prevented NEC in a neonatal rat model and was associated with lower NEC risk in a human clinical cohort study. Herein, gram-scale synthesis of two DSLNT analogs previously shown to have NEC preventing effect is described. In addition, four novel disialyl glycans have been designed and synthesized by enzymatic or chemoenzymatic methods. Noticeably, two disialyl tetraoses have been produced by enzymatic sialylation of chemically synthesized thioethyl β-disaccharides followed by removal of the thioethyl aglycon. Dose-dependent and single-dose comparison studies showed varying NEC-preventing effects of the disialyl glycans in neonatal rats. This study helps to refine the structure requirement of the NEC-preventing effect of disialyl glycans and provides important dose-dependent information for using DSLNT analogs as potential therapeutics for NEC prevention in preterm infants.

An efficient streamlined chemoenzymatic approach has been developed for gram-scale synthesis of Lewis a angtigen (Le a βProN 3 ) and a library of sialyl Lewis a antigens (sLe a βProN 3 ) containing different sialic acid forms. Intially, commercially available inexpensive N-acetylglucosamine (GlcNAc) was converted to its N′-glycosyl p-toluenesulfonohydrazide in one step. Followed by chemical glycosylation, GlcNAcβProN 3 was synthesized using this protecting group-free method in high yield (82%). Sequential one-pot multienzyme (OPME) β1-3-galactosylation of GlcNAcβProN 3 followed by OPME α1-4-fucosylation reactions produced target Le a βProN 3 in gram-scale. Structurally diverse sialic acid forms was successfully introduced using a OPME sialylation reaction containing a CMP-sialic acid synthetase and Pasteurella multocida α2-3sialyltransferase 1 (PmST1) mutant PmST1 M144D with or without a sialic acid aldolase to form sLe a βProN 3 containing naturally occurring or non-natural sialic acid forms in preparative scales.

A new ent-kaurene beta-D-glucoside was isolated from Rabdosia rubescens, together with the known compounds oridonin, ponicidin, and pedalitin. The structure of new compound was determined, on the basis of spectral data and X-ray crystallographic analysis, to be ent-7 beta,20-epoxy-kaur-16-ene-1 beta,6 alpha,7 alpha,14 alpha,15 alpha-pentanol 1-O-beta-D-glucopyranoside.

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