ALPHA-AMINOALKANOIC ACID AND REDUCTION PRODUCT

摘要

Alpha-amino-alkanoic acid derivs. (I) and their salts are new: R1 = aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, aromatic or heteroaromatic gp.; protected OH or OH etherified with an aliphatic, araliphatic or heteroaryl-aliphatic gp.; or SH etherified with an aliphatic gp.; and R2 = aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, araliphatic or heteroaryl-aliphatic gp.; or R1 and R2 together form a divalent aliphatic gp.; R3 = COOH opt. esterified with an aliphatic, araliphatic or araliphatic gp.; CHO; or CHOH; R4 = H; aliphatic or araliphatic gp.; or amino protecting gp.; R5 = H or aliphatic gp. Also claimed are starting materials (III) and their salts. R12, R13 = OH etherified with an aliphatic, araliphatic or aromatic gp., esp. lower alkoxy. Further claimed is the conversion of (I) into hydroxylated amino-alkanoic acid amides (II) comprising: i) condensing (I) where R3 = formyl (obtd. as required from (I) where R1 = opt. esterified COOH by redn. or from (I) where R1 = CHOH by dehydrogenation), R4 = amino protecting gp. and R5 = H with magnesium and a haloalkane (a) in the presence of 1,2-dibromobutane; ii) protecting the resulting aminoalcohol (b) and sepg. the diastereomer mixt.; iii) debenzylating the protected aminoalcohol (c) obtd. and oxidising the hydroxymethyl prod. to the acid (d) via the corresp. formyl cpd.; iv) reacting the acid (d) with an amine (e); and v) deprotecting the resulting protected amide (f) and opt. converting the prod. (II) into a different prod. (II). R4 = H; lower alkyl; or lower alkanoyl; R5 = H or, when R4 = lower alkyl, H or lower alkyl; R10 = lower alkyl; lower alkenyl; cycloalkyl; or aryl-lower alkyl; R11 = lower alkyl opt. substd. by OH (opt. aliphatically esterified or etherified), amino (opt. mono- or di-substd. by lower alkyl or mono-substd. by lower alkanoyl or N,N-disubstd. by lower alkylene (opt. substd. by OH, lower alkoxy or lower alkanoyl), opt. N-alkylated or lower alkanoylated aza-lower alkylene, oxa-lower alkylene or opt. S-oxidised thia-lower alkylene), opt. esterified or amidated COOH, di-COOH, COOH(OH) or COOH-cycloalkyl, CN, lower alkanesulphonyl, thiocarbamoyl or sulphamoyl (opt. N-mono- or N,N-di-alkylated) or C-bonded opt. hydrogenated and/or oxo-substd. heteroaryl; C-bonded opt. hydrogenated and/or oxo-substd. heteroaryl; or cycloalkyl. Q = divalent protecting gp.; X1 = halo.