Versatile Stereoselective Synthesis of Completely Protected Trifunctional α‐Methylated α‐Amino Acids Starting from Alanine

Abstract

A new route to completely protected a-methylated ci -amino acids starting from alanine is described (see Scheme). These derivatives, which are obtained via base-catalyzed opening of the oxazolidinones (2S,4R)-and (2R,4S)-2, can be directly employed in peptide synthesis. The synthesis of both enantiomers of Z-protected a methylaspartic acid p-(tert-buty1)ester (04-(1ert-butyl) hydrogen 2methylaspartates ( R ) or (S)-4a), a-methylglutamic acid y-(tert-butyl) ester (05-(tert-butyl) hydrogen 2-methylglutamate ( R ) -or (S)-4b), and of NL-bis-Bocprotected ci -methyllysine (N6,N6-bis[(fer~-butyloxy)carbonyl]-2-methy~~ysine (R)-or (S)-4c) is described in full detail.

Studies of 2-Substituted 1,3-Oxazolidin-5-ones and 1,3-Oxazinan-6-ones as Precursors for the Synthesis ofN-Alkyl-β-Amino Acids

“…Column chromatography was performed on the residue, eluting with 15% ethyl acetate-hexane to afford the oxazolidinone 15 as an oil (55% yield), which was identical in all respects with previously reported material. [16] N-Alkyl-a-amino Acids N-Benzyloxycarbonyl-N-decyl-acetic Acid 16…”

ChemInform Abstract: Structure and Reactivity of Five‐ and Six‐Ring N,N‐, N,O‐, and O,O‐ Acetals: A Lesson in Allylic 1,3‐Strain (A1,3 Strain).

“…geminally disubstituted heterocycles derived from c( -branched amino acids [14]. The heterocyclic rings in the N-benzoyl-and N-(methoxycarbony1)oxazolidines 9 and 10, and in the N-(benzyloxycarbony1)-dihydrothiazole S-oxide 11 (Figs.…”

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The X-ray structures of fifteen 1,3-imidazolidine, 1,3-oxazolidine, 1,3-dioxan-4-one, and hydropyrimidine-4( I H)-one derivatives are described ( Table 2) and compared with known structures of similar compounds (Figs. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. The differences between structures containing exocyclic N-acyl groups and those lacking this structural element arise from the A',' effect of the amide moieties.

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A new approach to vinyl glycine derivatives from (+)-(RS)-3-[(p-toluenesulfinyl)methyl]-1-oxa-4-azaspiro[4,5]decen-3-ene

“…1 They are also potential precursors to new a-branched a-amino acids as building blocks for the novo peptide design. 2 Their unique conformational properties have also been a matter of particular interest. 3 The majority of the synthetic efforts towards b,c-unsaturated amino acids have been specifically directed towards vinyl glycine, 4 with few reports describing routes towards other b,c-unsaturated amino acids.…”