Tunicamycin derivatives

During the period of this research, the application of our approach to a tunicamycin derivative was undertaken. Though the work was not pursued far enough to obtain tunicamine or tunicaminyluracil, the scope of the general reaction was expanded somewhat, and some of... 

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-... 

However, the most important applications of 0,Se-acetals are related to sugar and nucleotide derivatives [34-36]. For instance, the generation of anomeric radicals from 0,Se-acetals is a very popular approach. The preparation of C-disaccharides by an elegant 8-endo-trig cyclization involving two tethered monosaccharides has been reported [Eq. (15)] [37, 38]. In a related manner, a concise route to tunicamycin antibiotics has been developed the key feature of... 

As shown in Sec. I, uracils have represented, for more than 90 years, a class of compounds that continually attract organic chemists, biochemists, medicinal chemists, and photobiologists. Uracils were first detected as constituents of ribonucleic acids, from which they were prepared by hydrolysis. Nucleosides derived from uracil are called uridine, pseudouridine, and uridine phosphate, respectively. Recently, uracil moieties were detected in the antibiotic Tunicamycin (85JA7761). 

More recently, Danishefsky reported a fully synthetic route to tunicamin-yluracil (274) derived from tunicamycin (85JA7761) and hikosamine (284) (85JA7762). Cyclocondensation of the ribosederived aldehyde (260) (84JOC1955) (Scheme 35) with diene 259 under catalysis by Eu(fod)3 (83JA3716) afforded an 86% yield of the carbon-linked disaccharide 261. Ozonolysis of 261, followed by oxidative treatment and esterification, furnished the /3-hydroxy ester 262 and its benzyloxymethyl ether 263. 

The existence of natural complex nucleoside antibiotics has prompted interest in their syntheses [173]. These compounds are composed of a C5 extended ribonucleoside. This extra chain of two or more carbons carries chiral centers. Some of these nucleosides, like tunicamycins or octosyl acids, can be regarded as C-linked disaccharides and their syntheses are not straightforward. Liposidomycin constitutes another class of complex nucleosides, which has been partially synthesized using a Wittig chain extension at C5 of the furanose derivative 243 [174]. 

Ribosylation of isopropylideneuridine and subsequent manipulations led to the synthesis of 170 (R = H), which constitutes a part-structure of the liposidomycin class of antibiotics. The two isomers of 170 (R = CH2OH) were also prepared in synthetic sequences that involved ribosylation of D-allofuranose and L-talofuranose derivatives at 0-5, with introduction of uracil at a late stage. Molecular modelling was carried out of both liposidomycins and tunicamycin with the UDP-iV-acetylmuramic acid-pentapeptide that is the substrate for the enzyme (translocase) in bacterial cell wall biosynthesis that the antibiotics inhibit, and, in accordance with the predictions, only the 5-isomer of 170 (R = CH2OH) was a good inhibitor. ... 

In all cases, save the formation of the link sequence in the bacterial peptidoglycan, it is a transfer of A/-acetylglucosamine (as its 1-phospho derivative) to a phospholipid acceptor that is blocked by tunicamycin. 

Lehle, L. Tanner, W. (1976) The Specific Site of Tunicamycin Inhibition in the Formation of Dolichol-bound -Acetylglucosamine Derivatives , FEBS Letters, 71,167-70 Lehle, L. Tanner, W. (1978) Biosynthesis and Characterization of Large Dolichol Diphosphate-linked Oligosaccharides in Saccharomyces cerevisiad, Biochimica et Biophysica Acta, 539, 218-29... 

Tunicamycin V (formerly "A") (26) has been prepared, together with 3 minor components of the complex and other analogues in the key step, the glycosyl chloride (27) was condensed with the reducing amino-sugar derivative (28), which was then conventionally converted to (26). Another communication reports a total synthesis of polyoxin J (29), converting 4-0-benzyl-2,3-0-isopropy-lidene-L-threose to deoxypolyoxin C (30) on the one hand and to the 5-0-carbamoyl-polyoxamic acid derivative (31) on the other, these... 

The known bona fide CS enzyme inhibitors are natural product-derived substrate analogs, eg. polyoxin D, tunicamycin, and nikkomycin Z, Figure 2. These complex natural products inhibit the enzyme well, but express little in vivo insecticidal activity, presumably due to unfavorable ADME attributes. 

C23H36N4O15 608.555 The closely related Tunicamycin, Strepto-virudin and Corynetoxin complexes are all mixts. of N -acyl derivs of the same... 

The processing of placental peptide hormones synthesized in lysates containing membranes derived from tunicamycin-treated ascites tumour cells has been reported. The cleavage of a pre-glycoprotein, pre-human chorionic gonadotrophin, and the sequestration of the processed form within the membranes, occurs in the absence of glycosylation. Thus, in contrast to certain processing... 

Protected subunits of tunicamycins have been synthesized. Cyclocondensation of the aldehyde (20), derived from uridine, with the butadiene (21) gave the dihydropyrone derivative (22) after desilyl-ation, and by further manipulation, the tunicamycin subunit (23) (Scheme 2). ... 

The synthesis of tunicamycin V using a 2-azido-2-deoxy-D-galactose derivative as starting material for a multistep sequence has been described. ... 

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