Total synthesis of spirobenzylisoquinoline alkaloids. Part IV

Abstract

The stereoselective synthesis of the racemic forms of the spirobenzylisoquinoline alkaloids corydaine and yenhusomidine is reported.

Diasteroselektive Hydroxyalkylierungen in 1‐Stellung von Tetrahydroisochinolinen und Synthese von Aporphin‐, Protoberberin‐ und Phthalid‐Alkaloider

“…s, CH-0); 4,14-3,88 (m, CH2N); 3,98 (s, CH30); 3,93 (s, CH30); 2,89-2,88 (m. ArCH,); 1,36 (s, t-Bu). ',C-NMR (20 MHz,CDC13): 177.57;152,87;147,Ol;145,44;140,71;129,14;122,39;119,57;118,50;117,28;108,49;106,76;100,82;83,74;62,29;58,05;56,88;42,43;39,15;29,13;28,18. MS: 454 ( < 1, MC' + I), 260 (90), 176 (39,1), 57 (100).…”

“…H); 5,92 (d,J = 7,05,4,32 (d,J = 7,05,CHN); 3,84 (s, CH,O); 3,14-2,59 (m, ArCHzCH2N); 1,18 (s,. ',C-NMR (20 MHz,CDCI,): 177,23;147,06;146,32;135,59;134,63;130,69;129,14;128,65;126,82;125,32;118,88;113,44;110.73;77,77;58,49;55,72;39,65;38,76;29,24;27,09. MS: 370 ( < 0.1, M" + l), 267 (2,3), 152 (2,1), 132 (IOO), …”

Total synthesis of spirobenzylisoquinoline alkaloids. Part V. Generalized approach to the complete set of alkaloids

“…This provided the previous dimethoxy amine (66 mg) and the phenolic amine 16 (51 mg) as a foam with the following characteristics: ir: 2.88 (sharp), 3 The oxazolidine (20 mg, 0.054 mmol) was reduced with sodium cyanoborohydride (10 mg) in 10 mL of methanol in the manner described for the preparation of 3. (+)-Corpaine (17) was obtained as a solid (20 mg, 0.053 mmol) which, after recrystallization from methanol, had mp 252-255'C.…”

“…In our earlier work (2), a difficulty arose at this stage and severely limited the generality of the synthesis: the Eschweiler-Clarke reaction, which had worked well in the ochotensimine synthesis (I), failed to convert 14, the hydrolysis product of 12, to corydaine (3). Direct reduction of the N-formyl group of 12 to N-methyl was accomplished with lithium aluminium hydride but inevitably the ketone was reduced at the same time.…”

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

“…Such methods, however, are in the main long and tedious, often beset with poor yields and are not especially suited to the preparation of alkaloids of the corydaine-sibiricine type because some differentiation of the two oxygenated positions of the five-membered ring C would have to be tailored into the C/D synthon. Recently these difficulties have in fact been overcome in a synthesis of corydaine (13).…”