Total Synthesis of (−)-Salviasperanol

Abstract

The achiral enynone shown cyclized to produce a tricyclic dienone that was converted in six steps to (-)-salviasperanol.

Collective Syntheses of Icetexane Natural Products Based on Biogenetic Hypotheses

“…Ad ivergent, elegant, and short synthesis of 10 members of the icetexane family of naturalp roducts hasb een achieved in four to nine steps from abundant (+ +)-carnosic acid, isolated from Rosmarinus officinalis.O ft hese icetexanes, (+ +)-salvicanol (12), (À)-cyclocoulterone (1), (À)-coulterone (22), (À)-obtusinoneD (36), and (À)-obtusinone E( 37)h aveb een synthesized for the first time. As traightforward, inexpensive, and efficient sequence, consistingo ft he methylation and hydrogenation of rosemary ethanol extracts enriched with carnosic acid and related congeners, has been developedt oo btain the desired trimethyl carnosic acid 8 in high yield.…”

“…Majetich and Zou have already reported such as ynthesis of brussonol( 33)f rom 31 through the heating of ac oncentrated solution of 31 in Et 2 O( 60 8C, 40 h, 70 %). [22] Furthermore, the crucial role of silica gel was further substantiated experimentally when an acetonitrile or acetone solutiono fb russonol (33)w as stirred under oxygen atmosphere and only trace amountso fp rzewalskin E( 32)w ere obtaineda fter several days. [30b] However,n one of thesemethods was suitable for producing przewalskin E( 32)d irectly from 31.…”

Benefits of Unconventional Methods in the Total Synthesis of Natural Products

“…Somfai’s synthesis of anisomycin ( 51 ) 33 featured a vinylaziridine–pyrroline rearrangement. Njardarson’s synthesis of biotin ( 52 ) 34 featured a vinylthiirane–dihydrothiophene rearrangement, whereas salviasperanol ( 53 ) 35 was prepared by Majetich via vinyloxirane–dihydrofuran rearrangement.…”

Structure, biosynthetic relationships and chemical synthesis of the icetexane diterpenoids

“…Majetich and co-workers also reported the first asymmetric total synthesis of (-)-salviasperanol in late 2007 (Scheme 17). 80 Vinylogous ester 137 was reacted with lithium acetylide, and treatment of the resulting adduct with aqueous HCl provided enynone 138. Although a cyclialkylation of 138 to dienone 140 could be envisioned, Drieding models of this species indicated that the arene and alkyne moieties were not close enough to react, and in the event 138 could not be directly converted to 140.…”

“…89 Vinylogous ester 183 was converted to enynone 184 by treatment with Aren's reagent and subsequent acidic workup. As noted for the related enynone employed in the total synthesis of salviasperanol by Majetich et al (see Scheme 17), 80 direct cyclialkylation of 184 is not achievable due to the lack of proximity of the arene and alkyne moieties. However, Lindlar hydrogenation of 184 provided an intermediate dienone that was readily transformed to tricyclic dienone 185 on treatment with TiCl 4 or BF 3 $OEt 2 .…”