A New Synthesis of 3,6-Dialkyl-1,4-dimethyl-3,6-epithio-and -3,6-epidithio-2,5-piperazinediones

Abstract

A new route for synthesis of 3,6-dialkyl-1,4-dimethyl-3,6-epithio- (8) and -3,6-epidithio-2,5-piperazinediones (9) via the corresponding bromo derivatives was described. Bromination of 3,6-dialkyl-1,4-dimethyl-2,5-piper-azinedione with N-bromosuccinimide gave 3,3α,6,6α-tetrabromo (2) and 3,6-dibromo (3) derivatives, depending upon the straight chain (methyl, ethyl, propyl, butyl) or α-branched (isopropyl, sec-butyl) alkyl groups, respectively. After tentative substitution of 3,6-bromine atoms of 2 with methanol, 3α,6α-bromine atoms were reduced to give the corresponding 3,6-dialkyl-3,6-dimethoxy derivatives (5). Substitution of 3 or 5 with hydrogen sulfide in the absence or presence of zinc chloride, and successive oxidation with potassium triiodide gave 8 and 9 at the same time. Discussions were made on the structure of isomers and on the reaction mechanisms.

Free-Radical Reactions in the Synthesis of α-Amino Acids and Derivatives

“…Free radical reactions with molecular bromine or N -bromosuccinimide result in α-bromination, as illustrated in the reactions of the sarcosine derivatives 85a and 86a , to give the halides 85b and 86b , respectively. ,, In these examples, further reaction through loss of hydrogen bromide is not possible, but where there is an amino acid side chain with a β-hydrogen, the ionic elimination process often occurs subsequent to the radical bromination, to give dehydro amino acid derivatives which may react by bromine addition. Accordingly, the diketopiperazines 87a − d gave the corresponding dibromides 88a − d and tetrabromides 89a − d , from reaction with 2 and 4 equiv of N -bromosuccinimide, respectively, presumably via the reaction sequence shown in Scheme . Evidence in support of this sequence is provided from the reactions of related compounds.…”

Total syntheses of chaetocin and ent-chaetocin

“…Based on previous reports, in which hydrogen sulfide was reacted with a hemiaminal ether in the presence of ZnCl 2 , 30 we examined the substitution reaction using Lewis acids. Because BF 3 $OEt 2 is a widely used Lewis acid for the activation of hemiaminals and their ethers, we tested it in our case.…”

A Practical Sulfenylation of 2,5‐Diketopiperazines

“…NaNH 2 , S 8 , liq. NH 3 ) [6] or indirectly through their 3,6-dibromodiketopiperazine, [7] 3,6-dimethoxydiketopiperazine [8] and 3,6-dihydroxydiketopiperazine [9] derivatives. These methods require either harsh conditions or multi-step sequences, or both, and they lack in generality and efficiency.…”