Rearranged diterpenoids

The synthesis of the aromatic methyl ether (191) and the reduction of ring C has been studied." The backbone rearrangement of the synthetic intermediate (192) has been examined in the context of the synthesis of rearranged diterpenoids. The synthesis of the phenol (193), which is a degradation product of atisine, has been reported. 

Chang J, Xu J, Li M, Zhao M, Ding J, Zhang JS. Novel cytotoxic seco-abietane rearranged diterpenoids from Salvia prionitis. 

Distribution of Rearranged Diterpenoids from R elisabethae by Skeletal Class... 

Figure 4 (a) Distribution of all of the Pseudopterogorgia elisabethae diterpenoid variants by carbon skeletal class (total = 109 compounds), (b) Approximate breakdown of all the rearranged diterpenoids from P. elisabethae by skeletal type. 

Francisco, C., Banaigs, B., Teste, )., and Cave, A. (1986a) Mediterraneols a novel biologically active class of rearranged diterpenoid metabolites from Cystoseira mediterranea (Pheophyta). J. Org. Chem., 51, 1115-1120. 

Makinoa crispata (Steph.) Miyake from Japan was shown by Hashimoto et al. (1989) to contain diterpene derivatives of the sort illustrated as [466-469] (see Fig. 5.7 for stractures). More recently, Liu and Wu (1997) reported the presence of the rearranged abietane-type diterpenoid derivative makanin [470] from plant material of M. crispata collected on Taiwan. Of note was the apparent absence of any of these compounds in the Japanese plants. 

Liu, H.-J. and Wu, C.-L. 1997. A rearranged abietane-type diterpenoid from the liverwort Makinoa crispata. Phytochemistry 44 1523-1525. 

The key steps in the synthesis of the stemodane-type diterpenoids are again the retroaldol-aldol procedure. This was best demonstrated by the rearrangement of the ketal (103) to the epimeric alcohol (104), upon treatment with acid, in 60%... 

Anionic oxy-Cope rearrangement was also employed for the enantioselective total synthesis of compounds related to marine metabolites (equation 230)305 307, as well as for the preparation of diterpenoide vinigrol (equation 231)308 and cerorubenic acid-in... 

Another tetracyclic carbon skeleton, named cumbiane, has been isolated from Pseudopterogorgia elisahethae. Its representatives are the diterpenoids cumbiasin A (33) and B (34) [20] their structures and relative configurations were elucidated by interpretation of a combination of spectral data. The six-membered ring D was formed by connecting CIO and C16 of an elisabethane carbon skeleton. The carbocyclic skeleton of the cumbiasins is unprecedented and represents a new class of C20 rearranged diterpenes. The tricyclic seco-cumbiane skeleton is derived from the cumbiasins by cleavage of the C15-C16 bond. Due to intramolecular cyclizations two additional oxo-heterocycles are present in cumbiasin C (35) [20] (Fig. 7). 

It has been shown" that isomerization of the exocyclic allylic system of the five-membered ring D of kaurenols depends on the orientation of the C(15) hydroxyl group. The total synthesis of methyl atis-16-en-19-oate, a tetracyclic diterpenoid possessing a bicyclo[2.2.2]octane skeleton, has been accomplished" using a homoallyl-homoallyl radical rearrangement process of methyl 12-hydroxykaur-16-en-19-oate monothioimid-azolide (280) as the pivotal step. Two plausible mechanisms have been presented" ... 

IPP and DMAPP lead to geranylpyrophosphate (GPP), which is an immediate precursor of monoterpenes. The formation of nerylpyrophosphate (NPP) from GPP gives rise to a wide range of acyclic, cyclic, bicyclic or tricyclic skeletons. Reactions like rearrangement, oxidation, reduction and hydration via various terpene cyclases result in the formation of numerous terpene derivatives. Condensation of GPP and IPP leads to farnesylpyrophosphate (FPP), the immediate precursor of sesquiterpenoids. Likewise, FPP and IPP are conducive to diterpenoids. 

Head-to-tail rearrangement of four isoprene units results in the formation of diterpenes (C20H32), as seen also in Fig. 4.2. Diterpenes are generally found in resins, e.g. pimaric acid and abietic acid. Some diterpenoids are also constituents of essential oils, e.g. phytol [3, 7-14, 37, 52, 53]. Like sesquiterpenes, diterpenes are heavier than monoterpenes therefore, they require more energy to go to the vapour phase. For this reason, longer distillation times are necessary for their recovery. The DNP lists 118 different structural types for diterpenoids [37]. Important diterpenes found in essential oils will be detailed. Some representatives of volatile diterpenes are as in Structure 4.32. 

New diterpenoids belonging to weo-clerodane type (39), some having an unusual neo-clerodane rearranged skeleton with eight-membered ketone ring (40-44), were recently described126. 

There has been intense interest in recent years in selective modification of functionality in baccatin III, 1, the basic diterpenoid core of paclitaxel (Taxol ) which is now established as a clinically active antitumour drug. Given the complexity of 1, rearrangements are common even under mild conditions and attempts to carry out apparently simple transformations are frequently frustrated, as shown by the following example. The 13p-chloro derivative 2 was prepared and fully characterised, then treated with sodium azide in aqueous DMF at 60°C in the expectation that the 13 a azide would be obtained. The product, however, was shown to be the ring cleaved compound 3 (71% yield). 

Cyclization reactions of GGPP mediated by car-bocation formation, plus the potential for Wagner -Meerwein rearrangements, will allow many structural variants of diterpenoids to be produced. The toxic principle taxine from common yew (Taxus baccata Taxaceae) has been shown to be a mixture of at least eleven compounds based on the taxadiene skeleton which can be readily rationalized as in Figure 5.43, employing the same mechanistic principles as seen with mono- and sesqui-terpenes. 

The Mechanism of the Garryfoline-Cuauchichicine Rearrangement.—The acid-catalysed rearrangement of garryfoline (51) and of other C2o diterpenoid... 

In 1974, Japanese chemists (134) demonstrated the utility of 13C-NMR spectroscopy in the field of C20-diterpenoid alkaloids. They determined the structures of miyaconine (145) and apomiyaconine (147), two rearrangement products of miyaconitine, by the aid of 13C-NMR spectroscopy. 

A new approach to the abe ring system of the pentacyclic C20 diterpenoid alkaloids has been reported by van der Baan and Bickelhaupt.51 For the model system of major interest, (134) was prepared from (133) by reaction with cyano-acetamide. Treatment of (134) with allyl bromide gave almost exclusively C-alkylation, to afford (135). On heating (135) at 100—110°C, a Cope-type rearrangement to (136) was effected. This compound was then N-alkylated with ethyl iodide-DMF, the product being (137). Treatment of (137) with IV-bromosucc-... 

The beyerene diterpenoids isolated from Sideritis pusilla possess a C-l 4a-hydroxy-group. The 7,18-diacetate of pusillatriol (78) was prepared75 by rearrangement of the 15,16-epoxide of 7,18-diacetoxysideridiol, thus interrelating the two... 

The monoterpenes 5(-i-)-carvone (10 Scheme 2, Nicolaou et al.) and / (—)-a-phellandrene (20 Scheme 3, Danishefsky et al.) are chosen as the starting materials for the syntheses of the diterpenoid skeleton of eleutherobin (1). Again, both routes require the separation of diastereo-mers by chromatography. The addition of 1-ethoxyvinyllithium to the TBS-protected aldehyde 13 (Scheme 2) leads to a mixture of diastereomeric alcohols (5 4 ratio in favor of the desired configuration at C8), which is separated by Nicolaou et al. after the alkynylation with ethynyl magnesium bromide in a later step. 13 was synthesized in close analogy to Trost et al. with bond formation between C9 and CIO via Claisen rearrangement (Scheme 2) [17]. 

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