Synthesis of peptides by means of ethyl α‐chlorovinyl ether and α, α‐dichlorodiethyl ether

Abstract

,Ethyl a-chlorovinyl ether IV and a,adichlorodiethyl ether V can be used for the synthesis of ipeptides. The reactions are performed by refluxing a mixture of an acylamino acid I, an amino acid ester-hydrochloride I1 and one of the chlorinated ethers IV or V in ethyl acetate. Optically pure acyl peptide-esters VlIJ are obtained. The method has been applied mostly for the preparation of acyl dipeptide-esters, but higher peptides have also been obtained. Acylamino acid chlorides VI are most probably intermediates.One of us ,has reported 1) that a peptide bond can easily be formed between an acylamino acid I and an amino acid ester-hydrochloride 11, by refluxing a mixture of these two substances with ethoxyacetylene I11

4‐(Dimethylamino)pyridine N‐oxide (DMAPO): An Effective Nucleophilic Catalyst in the Peptide Coupling Reaction with 2‐Methyl‐6‐nitrobenzoic Anhydride

“…[c] >99 % ee (determined by HPLC with CHIRALCEL OD‐H). [d] [ α ]${{{21\hfill \atop {\rm D}\hfill}}}$ =−22.2 ( c =2.43, EtOH); reference [15]: −22.10 15. [e] [ α ]${{{27\hfill \atop {\rm D}\hfill}}}$ =−17.1 ( c =0.57, EtOH); reference [16]: −16.90 16.…”

“…15 :12, 15 Z‐ L ‐Ala‐Gly‐OEt: HPLC (CHIRALCEL OD‐H, hexane/ i PrOH=9:1, flow rate=0.5 mL min −1 , detect 254 nm), t R =28.7 ( L ), 36.2 min ( D ); 1 H NMR (CDCl 3 ): δ =7.39–7.28 (m, 5 H, Ph), 6.65 (br s, 1 H, 2‐NH), 5.40 (br d, J =7.4 Hz, 1 H, 2′‐NH), 5.06 (d, J =12.3 Hz, 1 H, Bn), 5.00 (d, J =12.3 Hz, 1 H, Bn), 4.24 (br dq, J =7.4, 6.9 Hz, 1 H, 2′‐H), 4.12 (q, J =7.1 Hz, 2 H, EtO), 3.92 (br d, J =5.3 Hz, 2 H, 2‐H), 1.32 (d, J =6.9 Hz, 3 H, 3′‐H), 1.19 ppm (t, J =7.1 Hz, 3 H, EtO); 13 C NMR (CDCl 3 ): δ =172.6 (C1′), 169.6 (C1), 155.9 (Z‐C), 136.1 (Ph), 128.5 (Ph), 128.1 (Ph), 128.0 (Ph), 67.0 (Bn), 61.5 (EtO), 50.4 (C2′), 41.2 (C2), 18.5 (C3′), 14.0 ppm (EtO).…”

Synthesis ofω-Substituted Alkanethiols and (Bromomethyl)methylthiomalonates

“…FC (CH 2 Cl 2 / H 9.58,N 4.19;found: C 56.26,H 9.70,ethoxy]acetic Acid (Dithiodipropane-3,1-diyl) Ester (11). According to [25], a mixture of 7 (4.58 g, 25.7 mmol), CHCl 2 OMe (3.7 g, 32.1 mmol) and ZnCl 2 (0.18 g, 1.2 mmol) was stirred at r.t. for 1 h and refluxed 1 h under N 2 . The excess of CHCl 2 OMe was evaporated, the residual acid chloride dissolved in CH 2 Cl 2 (10 ml) and added dropwise within 30 min to a soln.…”