Alkaloids mimicking the structures of monosaccharides are now believed to be widespread in plants and microorganisms, and these sugar mimics inhibit glycosidases because of a structural resemblance to the sugar moiety of the natural substrate. Naturally occurring sugar mimics with a nitrogen in the ring are classified into five structural classes: polyhydroxylated piperidines, pyrrolidines, indolizidines, pyrrolizidines and nortropanes. Glycosidases are involved in a wide range of important biological processes, such as intestinal digestion, post-translational processing of glycoproteins and the lysosomal catabolism of glycoconjugates. The realization that alkaloidal sugar mimics might have enormous therapeutic potential in many diseases such as viral infection, cancer and diabetes has led to increasing interest and demand for these compounds. Most of these effects can be shown to result from the direct or indirect inhibition of glycosidases. The glycosphingolipid (GSL) storage diseases are relatively rare hereditary disorders that are severe in nature and frequently fatal. Possible strategies for the treatment of these lysosomal storage diseases include enzyme replacement therapy, gene therapy and substrate deprivation. Recently, quite a new therapy for lysosomal storage diseases has been reported, namely a ‘chemical chaperone therapy’ for Fabry disease. In this report, the structural basis for the specificity of inhibition of alkaloidal sugar mimics and their current and potential application to biomedical problems will be reviewed.

Sugar-mimic glycosidase inhibitors: natural occurrence, biological activity and prospects for therapeutic application

Recent Developments of Transition-State Analogue Glycosidase Inhibitors of Non-Natural Product Origin

Photochemical reactions contribute in a significant way to the existing repertoire of carbon-carbon bond-forming reactions by allowing access to exceptional molecular structures that cannot be obtained by conventional means. In this Review, the most important photochemical transformations that have been employed in natural product synthesis are presented. Selected total syntheses are discussed as examples, with particular attention given to the photochemical key step and its stereoselectivity. The structural relationship between the photochemically generated molecule and the natural product is shown, and, where necessary, the consecutive reactions in the synthesis are illustrated and classified.

Photochemical reactions as key steps in natural product synthesis

Insofar as one of the fundamental objectives of organic synthesis is the construction of complex molecules from simpler ones, the importance of synthetic efficiency becomes immediately apparent and has been well-recognized.1 The increase in molecular complexity2 that necessarily accompanies the course of a synthesis provides a guide (and a measure) of synthetic efficiency. As a goal, one would like to optimally match the change in molecular complexity at each step with reactions of comparable synthetic complexity. Thus, the creation of many bonds, rings, and stereocenters in a single transformation is a necessary (though not sufficient) condition for high synthetic efficiency. The ultimate, perfect match would constitute single-step syntheses. More realistically, especially in view of the desire for general synthetic methods, the combination of mulScott E. Denmark was born in New York in 1953. He obtained an S.B. degree from MIT in 1975 and carried out research with Daniel Kemp and Richard Holm. His graduate studies at the ETH-Zurich with Albert Eschenmoser culminated with the D. Sc. Tech. degree in 1980. That same year he joined the faculty of the University of Illinois at UrbanasChampaign and was promoted to full professor in 1987. In 1991 he was named the Reynold C. Fuson Professor of Chemistry. His research interests are primarily in the invention of new synthetic reactions, structure and reactivity of organoelement reagents, and the origin of stereocontrol in fundamental carbon−carbon bond forming reactions.

Tandem [4+2]/[3+2] Cycloadditions of Nitroalkenes.

Rephrasing Fuson's original formulation, the principle of
vinylogy explains how the influence of a functional group may be relayed to a distant point in the molecule when these two sites are connected to by conjugated unsaturated linkages, such as double and triple bonds or aromatic moieties.
This principle has been applied, over the years, to the majority of polar carbon-carbon bond-forming reactions of various repute, including the venerable Michael addition reaction, where the electrophilic -CdX site (1,2-addition) is “usurped” by a remote conjugated -RCdCR-CdX position (1,4-addition). The aldol addition reaction and the related
Mannich process, both fundamental pillars of organic synthesis, have not escaped this fate, and both of their
vinylogous extensions have emerged as extremely valuable
synthetic methodologies.

The Vinylogous Aldol and Related Addition Reactions: Ten Years of Progress†

A new, stereocontrolled synthesis of cis,anti,cis-tricyclo[6.3.0.02,6]undecanes. Total synthesis of (.+-.)-hirsutene

Total syntheses of de-branched nagstatin and its analogs having glycosidase inhibiting activities

Stereoselective total synthesis of pyrrolizidine alkaloid bases: (-)-rosmarinecine and (-)-isoretronecanol

Asymmetric Vinylogous Mukaiyama Aldol Reactions Using Vinylketene N,O-Acetals in Total Syntheses of Natural Products

https://iopscience.iop.org/article/10.1016/j.stam.2006.05.001/pdf

Kuniaki Tatsuta

Papers

A new, stereocontrolled synthesis of cis,anti,cis-tricyclo[6.3.0.02,6]undecanes. Total synthesis of (.+-.)-hirsutene

Total syntheses of de-branched nagstatin and its analogs having glycosidase inhibiting activities

Stereoselective total synthesis of pyrrolizidine alkaloid bases: (-)-rosmarinecine and (-)-isoretronecanol

Asymmetric Vinylogous Mukaiyama Aldol Reactions Using Vinylketene N,O-Acetals in Total Syntheses of Natural Products

Total syntheses of bioactive natural products from carbohydrates