Enmein type diterpenoids

The NMR spectra of enmein-type diterpenoids in which 6a-H is part of a hemiacetal contain only a singlet assignable to this proton because of its ca. 90° dihedral angle with 5-H [e.g. isodocarpin (64), carpalasionin (77) in Table VIII, and enmein (62), isodotricin (65) etc. in Table II]. In spirolactone-type diterpenoids having a hemiacetal function 6-H is a doublet [e. g. trichorabdal E (96) in Table VIII and trichorabdals F (97) and G (98) in Table II]. In the enmein-type diterpenoids of this group, C-6 is R except for rabdosin A (73), while the spirolactone-type diterpenoids occur as a mixture of 6R- and 6S-isomers 81). Shikodonin has been reported to have structure (88) on the basis of X-ray analyses of its 6-O-methyl and 6-0-ethyl derivatives, but our experimental results are inconsistent with this proposal, and thus the stereochemistries of C-5 and C-6 in (88) seem questionable. 

Chemical reactions which were useful for structure determination of enmein-type diterpenoids involve removal or chemical transformations of the functional groups which are illustrated in Scheme 6. 

Table II. cnt-6,7 Secokaurane Type Diterpenoids a) Enmein Type...

The 6-hydroxy-7-hemiacetal structure which is common to oridonin-type and longikaurin C-type diterpenoids is oxidatively cleaved at the C-6, C-7 bond by periodate oxidation. If a hydroxyl is present at C-1, then relactonization occurs to give enmein-type diterpenes 36, 78). If no hydroxy group is present at C-1 (R = H or OAc in Scheme 3), then the oxidative cleavage gives spirolactone-type compounds [26, 36, 79, 80, see also III-5-(a)]. 

Before 1979, the only 6,7-secokauranes were of what we have called the enmein-type, but since then a number of spirolactone-type diterpenoids have been reported, the first being shikodonin (88). As shown in Table VIII, each group is classified into four types. NMR data for a representative of all eight types are also listed. 

E. Fujita and coworkers were interested in conversion of a 6,7-secokaurane type diterpenoid such as enmein to e /-abietane (123), a hydrocarbon unknown at the time. Alcohol (119) [derived from enmein (62) as shown in Scheme 16] was cleaved with NaH to an aldehyde, a ring-D open derivative. The latter was converted into a lactone ester (120) which was subjected to the acyloin condensation to give isomeric products (121) and (122). Both compounds were deoxygenated in four steps to give a hydrocarbon (123). On the other hand, starting from (—)-abietic acid and/or dihydroabietic acid, hydrocarbon (118) was prepared by the route shown in Scheme 17. The products (123) and (118) were shown to be enantiomeric, hence they were f-abietane and abietane, respectively (705). 

Kubota and coworkers reported high antibacterial activity for enmein (62), isodonal (71), nodosin (66), oridonin (32), and enmein-3-acetate (63) against Gram-positive bacteria (134) and showed that trichodonin (70), shikokianin (24), umbrosin A (1), and umbrosin B (2) inhibited the growth of Bacillus subtilis 134, 135). Shikokianidin (49) and the dihydro derivatives of the active diterpenoids were inactive, while their acetates retained the activity. It was therefore concluded that the a-methylene-cyclopentanone moiety was essential for antibacterial activity, the activity being attributed to a Michael-type addition of a sulfhydryl enzyme to this function (Scheme 40) 134). 

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