Preparation of E-1,3-diaminoethenyl functional groups by the reaction of enol tosylate of alpha-formylglycine with primary and secondary amines

Abstract

The E-1,3-diaminoethenyl functional group is a potentially useful synthon. A number of examples of E-1,3-diaminoethenyl functional groups were prepared in good yield starting from an E-enol tosylate of a serine based diketopiperazine and 1°-or 2° amine nucleophiles. The reaction proceeds via a stereoselective nucleophilic substitution pathway.

Feasibility study on the reaction of 1,4-diazabicyclo[2.2.2]octane (DABCO) with (L-Serine-L-Serine) and (L-Phenylalanine-L-Serine) diketopiperazines

“…The 1 H, 13 C, and COSY NMR spectra of 5 acquired in DMSO-d6 were consistent with the structure of ylidiene product. In the 1 H NMR spectrum, the signals at 4.95 and 5.30, and 6.75 ppm are assigned to the methylene and the vinyl groups, respectively.…”

“…18 According to the NOE correlations we have state that enol tosylate 4 adopts an E-stereochemistry of the double bond. 13…”

“…1 H NMR (400 MHz, DMSO-d6): δ = 3.6 (s, 6H), 5.0 (s, 2H), 8.0 (s, 2 NH's) ppm. 13 C NMR (100 MHz, DMSO-d6): δ = 56.8, 63.4, 166.0 ppm.…”

“…12 DKP derivatives, such as enol di-tosylate (2) and enol tosylate (4), can serve as building blocks for a class of important compounds called endiamino peptides [compounds bearing a 1,3-diaminoethenyl functional group]. 13 Endiamino bonds can induce a conformational rigidity in peptides and hydrogen bonding assisted enzyme sulfatases catalysis. It is worth to mention, that Callynormine A, is a recently isolated marine metabolite from Kenyan sponges Callyspongia abnormis, appears as a rare N-atom containing heterodetic peptide that has the Z-endiamino group as the key structural element that is proposed to induce conformational rigidity.…”

“…We have previously reported, that compound 4 undergo reaction with 1˚and 2˚ amines to yield products bearing 1,3-diaminoethenyl moiety. 13,18 However, when 3 equivalents of DABCO were used as a tertiary amine to react with compound 4 (Scheme 7), it resulted in a unique elimination bis-ylidiene product 5.…”