title: Asymmetric synthesis of tetrahydroisoquinolines by enzymatic Pictet-Spengler reaction.
abstract: Norcoclaurine synthase (NCS) catalyzes the stereoselective Pictet-Spengler reaction between dopamine and 4-hydroxyphenylacetaldehyde as the first step of benzylisoquinoline alkaloid synthesis in plants. Recent studies suggested that NCS shows relatively relaxed substrate specificity toward aldehydes, and thus, the enzyme can serve as a tool to synthesize unnatural, optically active tetrahydroisoquinolines. In this study, using an N-terminally truncated NCS from Coptis japonica expressed in Escherichia coli, we examined the aldehyde substrate specificity of the enzyme. Herein, we demonstrate the versatility of the enzyme by synthesizing 6,7-dihydroxy-1-phenethyl-1,2,3,4-tetrahydroisoquinoline and 6,7-dihydroxy-1-propyl-1,2,3,4-tetrahydroisoquinoline in molar yields of 86.0 and 99.6% and in enantiomer excess of 95.3 and 98.0%, respectively. The results revealed the enzyme is a promising catalyst that functions to stereoselectively produce various 1-substituted-1,2,3,4-tetrahydroisoquinolines.
authors.affiliation: a QOL Division Fine Chemicals Group Research Team, Kaneka Corporation , Takasago , Japan.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nishihachijo
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hirai
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawano
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Minami
authors.forename: Takane
authors.initials: T
authors.lastname: Katayama
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Yasohara
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sato
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Kumagai
mesh_terms: D019731:Carbon-Nitrogen Ligases / Q000235:genetics / Q000378:metabolism*; D060326:Chemistry Techniques, Synthetic; D039323:Coptis / Q000201:enzymology; D004926:Escherichia coli / Q000235:genetics; D055620:Optical Phenomena; D013237:Stereoisomerism; D013379:Substrate Specificity; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D044005:Tetrahydroisoquinolines; C014843:1,2,3,4-tetrahydroisoquinoline; D019731:Carbon-Nitrogen Ligases; C450500:norcoclaurine synthase
keywords: Pictet–Spengler reaction; isoquinoline alkaloid; norcoclaurine synthase