212070-56-9

Upstream product

• 28920-43-6 (fluorenylmethoxy)carbonyl chloride 
• 212070-55-8 tert-butyl N-<(1S)-2-methyl-1-<<<1,1-dimethyl-2--2-thioxoethyl>amino>carbonyl>propyl>carbamate 
• 13734-41-3 t-Boc-L-valine 
• 187884-05-5 (2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutanethioic S-acid 

Downstream Products

• 212070-57-0 (9H-Fluoren-9-yl)methyl N-<(1S)-2-methyl-1-<<<1,1-dimethyl-2--2-oxoethyl>amino>thioxomethyl>propyl>carbamate 

Relevant academic research and scientific papers

Synthesis of endothiopeptides by using the 'Azirine/Oxazolone method

The reaction of terf-butyl- or THP-protected mandelic thioacid (7a and 7b) with N,N,2,2-tetramethyl-2H-azirin-3-amine (2a) gave the dipeptide analogues tBu- and THP-Mns-Aibψ[CS]NMe2 (8a and 8b, resp.) with a C-terminal thioamide group. Treatment of 8a with HCI gas in toluene led to 2-(l-tert-butoxybenzyl)- 4,4-dimethyl-1,3- thiazole-5(4H)-one (9); which reacted with dimethylamine via ring opening to give tBu-Mnsψ[CSNH]Aib-NMe2 (11a), an isomer of 8a with the thioamide group within the chain, i.e., the product of a sulfur migration. In the case of 8b, selective deprotection of the THP-hydroxy group was achieved by treatment with pyridinium p-toluenesulfonate (PPTS) in ethanol. Cyclization of the resulting Mns-Aibψ[CS]NMe2 (13) yielded the 2-thioxomorpholin-5-one 10. In a similar manner, Boc-Val-SH (14) reacted with azirine 2b to give Boc-Val-Aibψ[CS]N(Me)Ph (15a), which was transformed to Fmoc-Val-Aibψ[CS]N(Me)Ph (15b) and further to Fmoc-Valψ[CSNH]Aib-N(Me)Ph (16) by treatment with ZnCl2 in acetic acid. Coupling of two of these molecules via the l,3-thiazol-5(4H)-one 17 yielded the endodithiopeptide Fmoc-Vaψ[CSNH]Aib- Valψ[CSNH]Aib-N(Me)Ph (19).

A novel acid-catalyzed isomerization of Aib-containing thiodipeptides

The use of amino thioacids in the 'azirine/oxazolone method' led to completely epimerized Aib-containing endothiodipeptides (Aib=2- aminoisobutyric acid). It could be established that the epimerization occurred during the acidic hydrolysis of the primaril

Synthesis of the endothiopeptide BOC-Trp-Ile-Ala-Aib-Ile- ValΨ[CSNH]Aib-Leu-Aib-Pro-OMe by a variation of the 'azirine/oxazolone method'

The synthesis of the decaendothiopeptide BOC-Trp-Ile-Ala-Aib-Ile- ValΨ[CSNH]Aib-Leu-Aib-Pro-OMe is described. The introduction of the thioamide group next to the bulky Aib occurred via a variation of the 'azirine/oxazolone method' without epimerisation. The structure of the decaendothiopeptide was established by single-crystal X-ray crystallography, thereby two types of helices could be observed.