Diastereoselective alkylation of (3S)- and (3R)-3-methylpiperazine-2,5-dione derivatives. A convenient approach to both (S)- and (R)-alanine

Abstract

Treatment of (3S)-3-methylpiperazine-2,5-dione 6a with LHDMS followed by alkylation of the corresponding enolate with methyl iodide affords (3S,GS)-3,6-dimethyl derivative 7 in 98% de. The same reaction sequence carried out on (3R)-derivative 6b leads to a 937 diastereomeric mixture of (3R,6R)-8a and (3R,6S)-8b. Cleavage of the heterocyclic ring of 7 and 8a with 57% HI leads to (S)-and (R)-alanine, respectively. The configuration at C-3 (of 68 and 6b) and at C-6 (of 7 and 88) can be assigned on the basis of 'H NMR spectroscopy and conformational analysis performed by MMPMI.

Inhibition of Mitosis by Glycopeptide Dendrimer Conjugates of Colchicine

“…Colchicine binds to tubulin and inhibits its polymerization (3) mediacy of the Boc derivative 2 to give deacetylcolchicine 3. [14] The amino group was then acylated to give either the 7-chloroacetamido derivative 4, [15] to be used for thioether bond formation with the core cysteine of the dendrimers, or the dithiopyridyl-propionyl derivative 5, [16] to be used for disulfide coupling to cysteine. Penta-O-acetyl-a-d-glucopyranoside (6) was converted to the corresponding bromide by reaction with hydrogen bromide, [17] and then glycosylated with N-hydroxyphthalimide under phase-transfer conditions, as described for the reaction with N-hydroxysuccinimide, [18] to give intermediate 7.…”

Studies towards the synthesis of bicyclomycin precursors: Synthesis of N,N′‐disubstituted 2,5‐diketopiperazines in solution and on solid phase

“…Tetrahydropyran-2-ol (7) exists in an equilibrium with 5-hydroxypentanal (8), thus could be used as an aldehyde equivalent [24,25]. Similarly, semicyclic N,O-acetals (9) exists in an equilibrium with imines 10 and as the imines can be functionalised to the respective linear products, e.g. amino-alcohols [26,27].…”

“…3-Substituted 2,5-DKPs (A, Scheme 1) represent peptidomimetics with interesting biological activity [3][4][5][6][7] and they may serve as precursors to the other versatile classes of compounds including: amino acids [8,9], bicyclic derivatives [5,[10][11][12] or piperazines [12][13][14]. Moreover, they serve as synthons in the course of synthesis of very important antibiotics like bicyclomycin (B, Scheme 1) [15] or quinocarcin [16].…”

Preparation of (R)‐ and (S)‐α‐methyldopa from a chiral hydantoin containing the α‐phenylethyl group

“…6,10 Under these conditions, both`a mide'' groups were cleaved and the phenethyl group was removed to give the desired amino acids, (S)-and (R)-2, in good yields (89À91% yield) of the free amino acid after ionexchange puri®cation (Scheme 8).…”