Syntheses Directed Toward Chasmanine

Syntheses Directed Toward Chasmanine.—Outstanding progress toward the total synthesis of the complex hexacyclic diterpenoid alkaloid chasmanine (46) has been reported. The pentacyclic intermediate (69) has been prepared, and, using a model system, the methodology for the conversion of this compound into chasmanine has been developed. These experiments employed many processes developed in the earlier synthetic work, and in a number of instances, considerable improvements in the methods have been made. 

For the synthesis of (69), the enol ether (71) from the indanone (70) was carboxylated with COa-n-butyl-Iithium in THF at —70 C to yield (72). The methyl ester (73) was converted into (75) via the maleic anhydride adduct (74), essentially as described in earlier work. Lithium aluminium hydride reduction followed by oxidation with dicyclohexylcarbodi-imide afforded the aldehyde (76). This was condensed with excess (77) to yield a mixture of the diastereomers (78). Oxidation with chromium trioxide-pyridine in methylene dichloride gave (79), which could be converted into the diketone (80) by treatment with excess benzenesulphonylazide. The diketo-lactam (81) was prepared from (80) as described for the synthesis of the analogous intermediate used in the synthesis of napelline. Reduction of (81) with lithium tri-t butoxyaluminohydride gave the desired dihydroxy-lactam (82). Methylation of (82) with methyl iodide-sodium hydride gave (83). Reduction of this lactam to the amine (84) with lithium aluminium hydride, followed by oxidation with potassium permanganate in acetic acid, gave (69). 

---

A New Synthesis of Chasmanine and 13-Desoxydelphonine 233 Syntheses Directed toward C20 Diterpenoid Systems 235... 

---