| 摘要 |
Production of alpha -lipoic acid from 1,3-propanedithiol comprises a multistep process culminating in the solvolysis of a 5-(1-oxo-1,3-dithian-6-yl)valeric acid derivative (VI). Production of alpha -lipoic acid comprises: (1) reacting 1,3-propanedithiol with an aldehyde or ketone of formula (Ia) or a (thio)acetal or (thio)ketal of formula (Ib) in the presence of a Lewis acid catalyst; (2) reacting the resulting 1,3-dithiane compound with an oxidizing agent to form a 1,3-dithiane 1-oxide of formula (II); (3) reacting (II) with acrolein in the presence of a base to form an allylic alcohol of formula (III); (4) reacting (III) with a trialkyl orthoacetate in the presence of an acid catalyst to form an allyl acetal of formula (IV); (5) heating (IV) at 60-145 deg C to form a 5-(1-oxo-1,3-dithian-6-yl)-4-pentenoic acid derivative of formula (V); (6) reducing (V) to form 5-(1-oxo-1,3-dithian-6-yl)valeric acid derivative of formula (VI); and (7) solvating (VI). R<1>, R<2> = H, A, Ar, pyridyl, 2-hydroxy-6-hydroxymethyl-3-methyl-4-pyridyl or benzyl; R<1>+R<2> = (CH2)n; A = 1-3C alkyl; Ar = phenyl optionally substituted with A, OA, NH2, NHA or NAA; n = 1-5; R = A, 1-3C acyl, trifluoroacetyl, benzyl or benzoyl; R' = H, A or benzyl; X = O or S; R<3> = A. Independent claim are also included for compounds (III)-(VI) and compounds of formula (IIIa). R'' = H, 1-3C alkyl, 1-3C acyl, aryl-substituted 1-3C alkyl or aryl-substituted 1-3C acyl. |
