Synthesis of Isoquinoline Alkaloids. Total Synthesis of (±)-Stylopine

Abstract

A total synthesis of (±)-stylopine [1], an alkaloid of the protoberberine type, was carried out using a 3,4-dihydroisoquinoline [2]-boron trifluoride complex and the propylenedithioacetal of methoxycarbonylpiperonal [31 as the main building blocks. The condensation product 4 was the key intermediate in the synthesis and was transformed either into stylopine [1] or 8-oxostylopine [51, as well as dihydrocoptisine [91- Stylopine (tetrahydrocoptisine) [!}, an alkaloid of the protoberberine type, was isolated for the first time in 1902 by Schlotterbeck and Watkins from Stylophorum diphyllum (1). Its structure was determined by Spath and Julian, who isolated it from Corydalis tuberosa (2). Since that time stylopine [1] in both the racemic and the optically active S-(~) form, has been found in many different plants of the families Fumariaceae and Papaveraceae (3).The protoberberine alkaloids play an important role as precursors in the biosynthesis of a variety of related isoquinoline alkaloids, such as protopines, phthalideisoquinolines, spirobenzylisoquinolines, rhoeadines, indenobenzoazepines, secoberbines, and benzo[c]phenanthridines. The transformations between these alkaloids have been reviewed by Hanaoka (4).The protoberberine system has been synthesized in many different ways and there are several reviews that outline various approaches to the synthesis of this class of alkaloids (5,6), including syntheses of stylopine [1] itself (7-11).In this paper we report a new and convergent synthesis of the protoberberine ring system from 3,4-dihydroisoquinoline [2] (12) and 1,3-dithiane [3] (13), according to a published synthetic strategy (13)(14)(15)(16)(17)(18). This method has already been successful in the syntheses of 1,2-secobenzylisoquinolines (14,15), secoberbines (13,16), secophthalideisoquinolines (17), and benzylisoquinolines (18). RESULTS AND DISCUSSIONReaction of the 6,7 -methylenedioxy-3,4-dihydroisoquinoline [2]-boron trifluoride complex (19), with the lithium salt of(2-methoxycarbonyl-3,4-methylenedioxyphenyl)-1,3-dithiane [31, resulted in formation of lactam 4 with the protoberberine carbon skeleton (Scheme 1).The ir spectrum of lactam 4, mp 267-268°, revealed a strong absorption band at 1650 cm \ characteristic of a -lactam. The *H-nmr spectrum indicated the presence

Cyclic azomethines and their hydrogenated derivatives. (Review)

“…Reactions of dihydroisoquinolines with organomctallic reagents deserve separate consideration. As might have been expected the addition of organolithium anions proceeds most readily [159,160]. The diastereoselective addition of sulfoxide anions enables asyrmnetric synthesis to be effecled, for example [160].…”

Canadine from Corydalis turtschaninovii Stimulates Myoblast Differentiation and Protects against Myotube Atrophy

“…Air-dried CT tubers were extracted with aqueous methanol and fractionated to obtain alkaloidal fractions using a conventional method. The alkaloidal fractions were subjected to SiO 2 column chromatography and six known alkaloids were isolated: stylopine ( 1 ) [ 16 ], corydaline ( 2 ) [ 17 ], canadine ( 3 ) [ 18 ], tetrahydropalmatine ( 4 ) [ 19 ], dehydrocorydaline ( 5 ) [ 20 ], and coptisine ( 6 ) [ 20 ]. Their structures were elucidated by a spectroscopic analysis and a comparison with previously reported data ( Figure 1 ).…”

Synthesis of 8‐Oxoberbines and Related Benzolactams by Pd(OAc)2‐Catalyzed Direct Aromatic Carbonylation

“…Colorless crystals (72%); R f 0.5 (5% methanol–dichloromethane); mp 267–270°C (methanol) (lit. [41] mp 250–252°C; lit. [22] mp 267–270°C).…”