Microstegiol, a rearranged diterpene from Salvia microstegia

An easy and stereoselective rearrangement of an abietane diterpenoid into a bioactive microstegiol derivative

“…Compound 3 had a molecular formula C 27 H 30 O 5 , as that of the starting material (2). The 1 H and 13 C NMR spectra of 3 (Table 1) were almost identical to those of microstegiol (1) (Ulubelen et al, 1992) and the observed differences were consistent with the presence in the former of a 4-hydoxybenzoyloxy group attached to the C-2 position instead of the C-2 methylene group of the latter. The HMBC correlations observed between the Me-20 protons and the C-5, C-6 and C-10 carbons, and between the Me-18 and Me-19 protons and the C-3, C-4 and C-11 carbons, as well as those between the 11-OH and the C-9, C-11 and C-12 carbons (Table 1), supported that 3 arises from the abietane skeleton of 2 by a 4(5 !…”

“…Microstegiol (1, Fig. 1) (Ulubelen et al, 1992) is a rearranged abietane isolated from several Labiatae plants belonging to the Salvia (Li et al, 2000;Topcu and Ulubelen, 1996;Ulubelen et al, 1992Ulubelen et al, , 1997 and Ajuga (Kö kdil et al, 2002) genera and it has shown pharmacological properties as an antileukemic, cytotoxic (Topcu et al, 2003) and antibacterial agent (Kabouche et al, 2005;Ulubelen et al, 2000). Surprisingly, only one total synthesis of the hydrocarbon framework of microstegiol (1) and its naturally occurring 3-oxo derivative (Chyu et al, 2005) has been reported until now (Taj et al, 2009).…”

Applications of the Nicholas Reaction in the Synthesis of Natural Products

“…The same group have also reported the total synthesis of the diterpene microstegiol [21,22], isolated from Salvia microstegia and possessing antileukemic activity [23]. The reaction of protected 3-isopropyl-2,7-naphthalenediol 22 (Scheme 5) with the same co- balt-alkyne complex 15 used earlier in the synthesis of velloziolide, under acidic conditions gave 23 after decomplexation with iodine.…”

Cyclohepta[de]naphthalenes and the Rearranged Abietane Framework of Microstegiol via Nicholas Reaction Chemistry

“…1,2 In particular, we have developed chemistry to incorporate nucleophiles, including electron-rich arenes, g to electron-withdrawing groups, 3 in an umpolung fashion, [4][5][6] and have used this chemistry to get access to seven-membered ring systems. 1a In this context we were drawn to cyclohepta [de]naphthalenes, featured in the rearranged abietanes such as microstegiol 7 and salvibretol, 8 and their oxygenated analogues ( Figure 1). 8,9 These compounds are isolated from a number of plants of the Salvia species that have long seen use as folk remedies and whose crude extracts have demonstrated antibacterial and anticancer activities; 10 microstegiol itself is known to possess antileukemic activity 7,11 and modest antibacterial activity.…”