Disulfide formation with pyridyl

For the synthesis of bombyxin IV (53) 192 regioselective formation of three disulfide bonds was achieved by exploiting the differentiated acid-stability of the 5-Trt vs the 5-tBu protection in 49 that allowed the air-mediated intramolecular disulfide formation in the A-chain (Scheme 23). For subsequent activation of the third cysteine residue from the precursor S-tBu derivative the rather drastic conditions of TfOH/TFA (1%) were applied in presence of di(2-pyridyl) disulfide which despite the strong acidity allowed a concomitant deprotection/ activation of this residue to give 50. Subsequent reaction of 50 with the B-chain derivative 51 established the intrachain heterodisulfide cross-link in 52 which on oxidation gave bombyxin IV (53). 

Alternatively, both peptide chains could be protected at one cysteine residue as a 5-Acm derivative and at the second cysteine residue by an acid-labile [Trt, Mob, Xan, or Bzl(4-Me)], base-labile (Fm), or reduction-labile (5-tBu) group. Both peptide chains may then be separately converted into the free thiol/Acm-protected form for selective activation of one chain as S-SPy or. S -Npys derivatives by reaction with di(2-pyridyl)disulfide or di[5-nitro(2-pyridyl)]disulfide, or as a sulfenohydrazide derivative by reaction with azodicarbocylic acid derivatives for formation of the first interchain disulfide bridge. 

The interesting antibiotics X-14S47A and A-23187 (calcimycin) contain a novel 2-ketopyrrole moiety, which is apparently important for biological activity. Nicolaou has developed a simple method for incorporation of this unit into the sensitive intermediates required for preparation of the natural products. Through use of the Mukaiyama protocol, formation of the 2-pyridyl tldol ester was effected with 2,2 -di-pyridyl disulfide and triphenylphosj iine. The reaction mixture was then cooled to -78 °C and was treated with a solution of pyrroylmagnesium chloride in THF (equation 21). 

Cosstick and co-workers have reported an improved procedure for the synthesis of phosphorothiolate-containing DNA using Arbuzov chemistry in which the nucleoside disulfides are generated in situ from the corresponding thioesters. Several nucleoside disulfides have been prepared and in particular the regioselectivity of reaction of these with a phosphite has been examined. The disulfide (59) allows the preparation of the desired diribonucleoside phosphoro-thiolate (60) but the reaction is accompanied by some (2-10%) formation of the pyridyl phosphorothiolate. 

The bis-2-pyridyl disulfide 232 is obtained by oxidation of the corresponding thione 234 with I2 in a basic medium. In combination with triphenylphosphane, it activates carboxylic acids in the formation of amides and esters. In this reaction, carboxylic acids are converted into pyridine-2-thiol esters 233 as intermediates ... 

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