A novel oxidation stage in the chemistry of protoberberine alkaloids. Synthesis of 7,8-dehydroberbines

Cerasodine and Cerasonine: New Oxoprotoberberine Alkaloids from Polyalthia cerasoides

“…As indicated in Figure , the hydroxyl group of 4 was first protected with an acetyl group (Ac 2 O in pyridine) to give the monoacetate 4a , which was then submitted to a controlled oxidation by iodine , to afford 4b as an intermediate. Treatment of 4b with 20% aqueous KOH led to the 7,8-dihydro-8-oxoprotoberberine ( 5 ), with simultaneous deacetylation.…”

“…10-Demethylxylopinine monoacetate, ( 4a ) (4.2 mg, 0.011 mmol) was dissolved in MeOH (10 mL) with stirring, and iodine (7 mg, 0.028 mmol) was added. The mixture was refluxed for 4 h, cooled to room temperature, and several drops of saturated Na 2 S 2 O 3 were added to reduce excess iodine . The reaction mixture was evaporated to eliminate the MeOH, and the aqueous portion was extracted with CH 2 Cl 2 (3 × 15 mL).…”

Bischler−Napieralski Cyclization−N/C-Alkylation Sequences for the Construction of Isoquinoline Alkaloids. Synthesis of Protoberberines and Benzo[c]phenanthridines via C-2‘-Functionalized 3-Arylisoquinolines1

“…Convenient approaches to the target protoberberine and benzo[ c ]phenanthridine derivatives via Bischler−Napieralski cyclization− N / C -alkylation sequences have been developed. It has been demonstrated that reactions of C-2‘-functionalized 1,2-diarylethylamides under Bischler−Napieralski cyclization conditions allow the one-pot preparation of 2,3-disubstituted 13,14-dihydroprotoberberines, which could not be synthesized by direct oxidation of the corresponding tetrahydroprotoberberines, and represent additional examples of this novel oxidation stage in the chemistry of protoberberine alkaloids. In addition, the Bischler−Napieralski reaction of C-2‘-functionalized 1,2-diarylethylenamides constitutes a very direct route into planar 8,9-dialkoxylated benzo[ c ]phenanthridinium salts in a reduced number of steps (three to four steps from keto acid 4 , one more from commercial homoveratric acid), with comparatively high overall yields.…”

Chemoenzymatic Cascades toward Methylated Tetrahydroprotoberberine and Protoberberine Alkaloids

“…The unpurified THPB 4b (formed from 3c ) was also heated in DMF at 120 °C for 18 h with 86% of starting material converted by HPLC, and this gave 5 as the only product in 21% isolated yield. This is a useful route to PBs from the analogous THPB, avoiding the addition of oxidase enzymes or oxidants (I 2 /EtOH, reflux) . Since the stereochemistry is lost during this oxidation, the racemic THIQ starting material could also be formed by a phosphate-mediated PS reaction which has been shown to be regioselective with α-methyl substituted aldehydes .…”

“…This is a useful route to PBs from the analogous THPB, avoiding the addition of oxidase enzymes 49 or oxidants (I 2 /EtOH, reflux). 50 Since the stereochemistry is lost during this oxidation, the racemic THIQ starting material could also be formed by a phosphatemediated PS reaction which has been shown to be regioselective with α-methyl substituted aldehydes. 24 The PB scaffold is synthetically useful, as the iminium ion is susceptible to nucleophilic attack, leading to C-8 functionalization.…”