Thioamides thioacylation

A large body of work has been directed toward synthesis and applications of thioamides. The most important uses are as synthetic intermediates " and in heterocyclic synthesis. " Among the wealth of synthetic methods that lead to thioamides, thioacylation routes are certainly of prime importance. 

Fluorinated dithioester 39 has also been involved in thioacylation reaction of enantiopure aminoalcohols leading to the corresponding hydroxylated thioamides. The later, treated either by SOCVpyridine, CH3SO2CI, or PhjP/DEAD, cyclise into thiazolines 42 without epimerisation and in excellent yields. An interesting application of this reaction is the synthesis of a new type of modified nucleotides such as 43 and 44 by a one pot reaction simply by mixing the dihydroxy substituted thioamide (obtained from 39 and the 2-amino-l,3-... 

The use of benzimidazolone derivatives 4, prepared from the anilides 3, for the thioacylation of peptides (Scheme 4) have also been reported, 27 and three thioamide analogues of tuftsin were prepared. Due to the acid lability of thioamides, Boc deprotection with SnCl4 represents a mild alternative for N-terminal extension.12 ... 

Peptide dithioesters have been used as model compounds to study the conformations of dithioacyl enzyme complexes. 1 3 Dithioesters are also used as thioacylating agents that introduce the thioamide bonds into the peptide backbone in order to study the structures of endothiopeptidesJ4,5 ... 

A second route involves preforming first the allylic halide addition to form the iminium salt arising from the alkylation on the highly nucleophic sulfur atom. Subsequent treatment with triethylamine provided the S-allyl thioimidoester which was usually not observed but underwent a deprotonation and a fast [3,3] sigmatropic transposition to give the a-allyl thioamide. With pyroglutamate derivatives no diastereoselectivity was found. An analogous sequence [197] was used with a thioacyl proline derivative, with some stereoselectivity. 

The synthesis of (+)-curacin A 271 was accomplished by a selective and facile thioacylation of amino alcohol 268 with the benzotriazole thioamide 269 followed by cyclization of 270 using Burgess reagent (Scheme 108) <1998TL2861>. 

Phenyldithioacetic acid (8) allows thioacylation of the 7-amino group in penicillanate (9) the resulting highly nucleophilic thioamide (10) gives intramolecular trapping of the sulfenic acid, RSOH, which is in thermal equilibrium with the thiazolidine 5-oxide moiety in (10 Scheme 2). ... 

Thioamide synthesis from dithiocarboxylates and amines under basic conditions gives thiols as rather unpleasant parallel products. This problem is avoided by using S-thioacylated thioglycolic acids (17), as... 

Alknyl silyl sulfides, R C=CSSiR 3, which are readily obtained by silylation of anions (39), react as thioketene equivalents. Thus, (3-thiolactams are formed in the reaction with C=N systems (c/. Volume 5, (Chapter 2.2) and thioamides on addition of amines equation (18) shows a typical example. This approach has great promise for the thioacylation of very sensitive natural products. 

Recently, a mild, efficient and racemization-free route for the incorporation of a thioamide linkage into a peptide either in solution or on solid phase was provided by Shalaby et al. [127], First, the N-Boc-amino acid anilide derivative was thionylated with P4St0 and subsequently activated by transformation to the benzotriazole derivative, affording a stable thioacylating reagent (Scheme 7.8) suitable for combinatorial syntheses. 

Thioacylation of amines have been developed as a synthetic method for thioamides. Various thioacylating agents can be used. The dithioic acid salts 41, which are generated in situ from organolithium or Grignard reagents with CS2,... 

Thioacylation can be effected by the reaction of indoles such as compound (37) with ethoxy-carbonyl isothiocyanate to give the 3-substituted ethoxycarbonyl thioamide (38) (Equation (7)) <93TL3797>. 

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