Cryptostyline

There are only two groups of alkaloids that appear to be derived from tyrosine (25, R = OH) utilized as a Cg—C2 fragment and a Cg—Cj unit which comes from phenylalanine (25, R = H). The first is that small group found only in the Orchidaceae, exemplified by cryptostyline I [22324-79-4] (67, from Cryptostylisfulva Schltri) C29H22NO4. 

The 1-phenyltetrahydroisoquinolines cryptostyline I (7) and cryptostyline II (8) have been synthesized by the condensation of 3,4-dimethoxyphenylethyl-amine with piperonal and veratric aldehyde respectively, followed by treatment with ethyl chloroformate and reduction with lithium aluminium hydride.21... 

Polniaszek and Dillard [26] reported the stereospecific synthesis of S-(-l-)-cryptostyline. The key step is the stereoselective addition of the protected aryl Grignard reagent to the iminium salt (see Table 3, entry 2). The 2-substituted tetrahydraisoquinoline was obtained as the S-isomer in 100% optical purity. 

The cryptostylines and their analogues have been used as pharmacological probes, such as the Dj dopamine receptor, an antagonist of substance P, and a peptide neurotransmitter. Propose a catalytic asymmetric synthesis of (S) (+) cryptostyline II starting from methyl 2 (2 formyl 4,5 dimethoxyphenyl)acetate and 4 bromo 1,2 dimethoxybenzene. 

The number of alkaloids based on the 1-substituted tetrahydroisoquinoline skeleton is legion and the structural variation which this skeleton affords, particularly in the case of 1-benzylisoquinolines, is rich. The 1-substituted isoquinoline skeleton of each kind probably arises by the common step of condensing a j8-arylethylamine with an appropriate carbonyl compound, for which the Pictet-Spengler reaction provides an analogy. In some cases the participation of a carbonyl compound is established but in others it is still speculative. Recently progress has been made in this area in studies on the biosynthesis of lophocerine, the Papaver alkaloids, and to some extent the cryptostyline alkaloids with their novel 1-phenylisoquinoline structures. 

Both dopamine and vanillin (but not isovanillin) serve as precursors for the remaining Ce-Cj residue in cryptostyline-I. The incorporation of vanillin was at a low level, but this was attributed to poor absorption into the plant. Protocatechual-dehyde, the known precursor for the Q-Ci unit found in the Amaryllidaceae alkaloids, has not yet been tested as as a precursor. 

Cryptostylis erythroglossa Cryptostyline I, Cryptostyline II, Cryptostyline III, 1 -(3,4-Methylenedioxyphenyl)- ... 

Phenyltetrahydroisoquinolines.—(+ )-Cryptostyline I, II, and III (227)—(229) have been synthesized by the Bischler-Napieralski approach followed by a resolution using (—)diacetone-2-keto-L-gulonic acid, and reductive N-methylation. The o.r.d. and c.d. spectra have been described in detaiP and the absolute configuration has been confirmed by an 2f-ray analysis of unnatural ( —)-crypto-styline II.HBr. ... 

Takano S, Suzuki M, Kijima A, Ogasawata K (1990) Synthesis of racemic cryptostylines I, II, and III by radical cyclizatiort. Chem Lett 315... 

Phenyltetrahydroisoquinoline alkaloids. Rare structures that only occur in orchids (Orchidaceae), e. g., cryptostyline I C 9H2,n04, Mr 327.4, mp. 101-102°C, [aJo +56° (CHCI3) from Cryptostylis... 

Dimers and Oligomers of Isoquinoline Alkaloids Cryptostyline Alkaloids Distribution of Isoquinoline Alkaloids Biological Activity... 

Fig. 32.4. Proposed biosynthesis of cryptostyline alkaloids (modified from Lundstrom, 1983 used with permission of the copyright owner. Academic...

The full details of the X-ray crystallographic analysis of the synthetic / -isomer of cryptostyline II have been published along with an added proof of its stereochemistry by the aromatic chirality method. ... 

Further proof of the -configuration of the natural cryptostylines was derived from the X-ray crystallographic analysis of ( —)-cryptostyline I. ... 

Leander and his group have demonstrated that labeled tyrosine and dopa as well as tyramine and dopamine, are specifically incorporated in low yields into cryptostyline in C. eryihroglossa. In addition, 3-hydroxy-4-methoxy-phenethylamine was incorporated more efficiently than the 3-methoxy-4-hydroxy... 

Dopamine has been shown to serve as the origin of both aromatic rings as well as the C-1 carbon of cryptostyline I. Degradation of isotopical crypto-styline I, obtained by feeding dopamine labeled at the j8-carbon, revealed that the C-4 atom accounts for only one half of the incorporated radioactivity. The remainder was presumed to reside at C-V ... 

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