Tunicamycins synthesis

Scheme 18. Silicon-directed radical cyclization in Myers s synthesis of (+)-tunicamycin V (97).

Methylene sugars are versatile starting compounds for the synthesis of aromatic and hydroxymethyl C-glycosyl compounds (71) and of double-ended C-glycosyl compounds (70). The double bond undergoes 1,3-dipolar cycloadditions to give isoxazoline derivatives (71), such as that used as a model for the synthesis of tunicamycin. Also, reaction with iodonium sym-... 

ST 13 fibroblasts maintained in a medium containing insulin differentiate into adipose-like cells. This conversion is characterized by the appearance of lipid droplets in the cytoplasm and by an increase in synthesis and accumulation of cellular triglyceride. The insulin binding increases about 10-fold during differentiation. Tunicamycin inhibits the differentiation and suppresses insulin-binding activity.551... 

Human-leukemic antigen (HLA-DR) has been found in remarkably low proportions on the plasma membrane of human, lymphoblastoid cells. In the presence of tunicamycin, both subunits of this cell-surface antigen showed lower apparent molecular weights. One of them completely lost its [3H]-labelled 2-acetamido-2-deoxy-D-glucose portion, implying that HLA-DR antigens possess oligosaccharides whose synthesis is lipid carrier-dependent.555... 

A special example of cell-cell interaction is the adherence of group B streptococci to canine, epithelial cells that are infected with influenza A virus. However, this capacity was blocked in the presence of tunicamycin, and this result supports the concept that adherence of streptococci to mammalian cells involves recognition of viral hemagglutinin, or its carbohydrate complement, the synthesis of which is blocked by tunicamycin.556... 

The biosynthesis in yeast of two enzymes that are D-mannoproteins has been studied. A membrane-associated isozyme of invertase (EC 3.2.1.26) has been shown to be a precursor of the external invertase.190 Its molecular weight, as determined by SDS-poly(acrylamide) gel electrophoresis, is 50,000, that is, smaller than that of the external invertase, and it correlates well with the presence of only the inner-core sugars of the final form. It is strictly bound to membranes, possibly those of the endoplasmic reticulum, and it can be completely split191 by endo-/3-N-acetylglucosaminidase H (EC 3.2.1.30). The addition of tunicamycin, which specifically inhibits formation of d-GIcNAc-PP-DoI, inhibits synthesis of external invertase, as well as further formation of the membrane-associated form, which completely disappears after addition of the antibiotic.190 In these aspects, the synthesis of this extracellular enzyme follows the pathway for secreted glycoproteins in animal systems. 

Although synthesis of apoprotein B-lOO is necessary for VLDL secretion, addition of carbohydrate moieties in the Golgi apparatus does not appear to be required, since blockage of this function by tunicamycin does not reduce VLDL secretion. 

The liposidomycins are a family of novel lipid-containing nucleoside antibiotics that were found in the culture filtrate and mycelia of Streptomyces griseoporeus These antibiotics, which have unique biological activity and structures, inhibit the formation of the lipid intermediate in bacterial peptidoglycan synthesis three times more than does tunicamycin and have extremely high specificity. The structures of liposidomycins B (1) and C were proposed on the basis of degradation and spectroscopic studies. They are identical except for slight variations in the lipid portion. 

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