Synthesis and Biosynthesis of Spirobenzylisoquinoline Alkaloids

Abstract

Abstract. The synthesis and biosynthesis of the spirobenzylisoquinoline alkaloids is reviewed. The methods of synthesis are discussed under four headings: from indan ones, from protoberberines, from phthalideisoquinolines, and miscellaneous methods.

C19 Benzylisoquinoline Alkaloid with Unprecedented Architecture from Hypecoum erectum

“…Since compound 1 features an unprecedented C19 BIA skeleton, a biosynthetic pathway of 1 together with two coisolates was proposed (Scheme ). As mentioned above, the normal C 16 BIAs (such as armepavine) are synthesized by condensation of dopamine and 4-hydroxyphenylacetaldehyde, which could be both derived from l -tyrosine. , With the key involvement of berberine bridge enzyme, − C 16 BIAs could be transformed to C 17 BIAs, such as epiberberine and N -methylsinactine. , Stevens rearrangement of a tetrahydroprotoberberine N -methyl salt precursor ( N -methylsinactine) would produce C 17 spiro-BIA, − such as sibiricine. , The C 17 spiro-BIA derivative is attacked by asparagine and through dehydration and dehydrogenation could produce rare C 21 spiro-BIA, such as hyperectine . The sibiricine analogue may undergo enzymatic reduction and ring-opening reaction to produce a benzaldehyde derivative.…”

A versatile synthesis of spirobenzylisoquinoline and phthalideisoquinoline alkaloids. Conversion of a phthalideisoquinoline to spirobenzylisoquinolines

“…( f ) -F h u s o m i n e ( 2 ) Sod~urn borohydride (150 mg) was added to a solution of yenhusomidine 6 (60 mg) in tetrahydrofuran (15 mL) and methanol (5 mL) and stirred for 24 h. The solution was acidified and the solvent removed under reduced pressure. The residue was basified (NH40H) and extracted with ether.…”