The synthesis of Ambrox®-like compounds starting from (+)-larixol

The oxidation of the (3-hydroxy-3-methyl-4-pentenyl)-side chain at C(9) of some labdanic diterpenoids with potassium permanganate was investigated. Triols, ketones, or cyclic enol ethers are the main reaction products, strongly influenced by the substituent at C(8). Further degradation of the methyl ketones by the Baeyer-Villiger reaction and modification of the exocyclic 8(17) double bond lead to suitable intermediates, which have been transformed into Ambrox((R))-like compounds. Synthetic routes using palladium catalyzed elimination or isomerization of allylic acetates, followed by ozonolysis have been developed as well for shortening of the side chain of (+)-larixol. Products from both routes have been cyclized to 6 alpha -hydroxy Ambrox((R)). This compound was used as the key intermediate for the synthesis of several other Ambrox((R))-like compounds of which some showed pleasant odour properties. (C) 2001 Elsevier Science Ltd. All rights reserved.