Sesquiterpenoid intermediate

Scheme 7 Diels-Alder reaction of a single precursor proceeds via different transition states that produce two isomeric intermediates, each of which can be converted to one of the enantiomers of the novel Tynacantha marginata sesquiterpenoid [64]...

Examining the structures of the sesquiterpenoid carbazole alkaloids, tubingensins A (379), B (380), aflavazole (381), and dihydrotubingensins A (382) and B (383), it is likely that they are biogenetically related, and could have originated from a common intermediate, nominine (448) (394). This hypothesis was supported by the isolation of nominine (448) and 20,25-dihydrooxyaflavinine (452) from the sclerotia of the same Aspergillus spp. (347). 

The structure of simularene (123), a new structurally interesting sesquiterpenoid isolated from soft coral (Simularia mayi), has been established by A-ray analysis. It has been suggested that the cyclosesquifenchene skeleton of simularene (123) is derived by rearrangement of the intermediate (122) proposed in the biosynthesis of a-and /8-copaene (124). 

A new elegant stereoselective synthesis of humulene (192) has been achieved by a route (Scheme 22) in which the 11-membered-ring framework [cf. (191)] is produced by cyclization of the 11-allylpalladium complex derived from intermediate (190). Buddledin-A (193), -B (194), and -C (195) are new piscicidal sesquiterpenoids which have recently been isolated from the root bark of Buddleja davidiC The caryophyliane framework of these compounds has been established by spectroscopic data and X-ray analysis of the mono-bromohydrin (196) derived from buddledin A (193). An extension of previous studies on the cyclization of the epoxy-ketone (197) derived from caryophyllene has shown that the base-catalysed cyclization of the isomeric epoxy-ketones (198) and (199) provides compounds... 

Scheme 23. A schematic representation of the postulated involvement of a protoilludane intermediate (213) in the biosynthesis of various sesquiterpenoid...

The spiroketone (347), previously used as an intermediate in the synthesis of several vetispirane sesquiterpenoids (cf. Vol. 5, p. 79) has been converted into ( )-solavetivone (337) by the sequence of reactions shown in Scheme 31. ... 

Collado and co-workers made detailed studies of the chemistry of the sesquiter-penoid caryophyllene and its hydroxylated products including rearrangements in-duced by superacids. They have recently reported novel rearrangements of the sesquiterpenoid panasinsane derivatives 213 to provide three products and interpreted the transformations by the involvement of the common carbocationic intermediate 214 [Eq. (5.304)]. 

An excellent review of the isolation, structural elucidation, total synthesis, and postulated biosynthesis of sesquiterpenoids based on the spiro[4,5]decane (vetis-pirane) skeleton has been published." Further studies on the development of alternative routes to the vetispirane sesquiterpenoids have been described. In one report100 the spirocyclic acetal (217), previously used as an intermediate in the synthesis of (—)-a-acorenol (218),101,102 has been converted into (—)-agarospirol (219) and (-)-/3-vetivone (220) by the reaction sequence outlined in Scheme 26. 

The C-2 trimethylsilyl-derived pyridino[7]furan was treated with the combined reagent NIS/KF to give 2-iodopyrido[ ]furan, a key intermediate for the synthesis of sesquiterpenoid furanoeudesmanes (NIS = A -iodosuc-cinimide) (Equation 69) <2003T325>. 

The cytotoxic sesquiterpenoid (-)-quadrone, isolated from the fungus Aspergillus terreus, possesses the constitution and absolute stereochemistry shown in (218). The tricyclic carbon skeleton of this interesting natural product is the same as that found in compound (198), which, as described above (Scheme 28), is readily prepared by thermolysis of the tricyclic diene (197). Thus, it appeared that the Cope rearrangement of a suitably substituted and functionalized derivative of (197) might serve effectively as a key intermediate in a total synthesis of ( )-quadione (218) that is, successful Cope rearrangement of a substrate, such as (219), would provide, stereoselectively, the tricyclic substance (220). Presumably, the intermediate (220) could then be converted into the keto aldehyde (221), which had already been transformed into ( )-quadrone (218). ... 

Hemiterpenoids are produced from the isoprenyl diphosphate DMAPP. All other terpenoids are produced from DMAPP and IPP via longer-chain prenyl diphosphate intermediates formed by prenyl transferases. Prenyl transferases (20) catalyze the formation of geranyl diphosphate (GPP), famesyl diphosphate (FPP), and geranylgeranyl diphosphate (GGPP) from one molecule of DMAPP and one, two, or three molecules of IPP, respectively (Fig. 1). Isoprenyl diphosphates are the substrates for all TPS, which lead to the hemiterpenoids, monoterpenoids, sesquiterpenoids, and diterpenoids, which will be highlighted with selected examples in the following sections. 

A pair of reductive eliminations on chlorohydrin intermediates was used to achieve regioselective introduction of alkene functionality in a synthesis of (18), a precursor of the sesquiterpenoid pentalenene (Scheme 7). Key steps in Tochtermann s synthesis of [6]-paracyclophane derivative (21 Scheme 8) were bromination of the bridged oxepine (19) followed by reductive elimination of the resultant dibro-mooxirane (20). 

Prezizaene (119) and the related tricyclic sesquiterpenoids (120)—(122) have been isolated from Eremophila georgii. The absolute stereochemistry of these compounds is antipodal to that of the zizaene sesquiterpenoids found in vetiver oil cf. Vol. 3, p. 123 Vol. 4, pp. 94—96) and their biosynthesis probably involves cyclization of 8-acoradiene (115) and rearrangement of the intermediate allocedryl (116) or cedryl (117) carbonium ions or their biological equivalents cf. Scheme 14). ... 

Epoxytrichothec-9-ene (138) (cf. Vol, 4, p. 90), a metabolite of T. roseum and a proposed intermediate in the biosynthesis of trichothecene sesquiterpenoids cf. Chapter 6), has recently been synthesized (Scheme 16). The final cyclization step [(136) (137)] in the synthesis is identical to that proposed in the biosynthesis... 

A protoilludane intermediate (225) (c/. Vol. 4, p. 113) has been implicated in the biosynthesis of protoilludane, illudane, illudalane, and marasmane sesquiterpenoids... 

In summary, these important investigations have rationalized the stereochemistry of the 1,3-hydride shift (which transfers a positive centre from C-10 or C-11 at the distal end of FPP to C-1 and so allows initiation of further isomerization or a second cyclization of the Cio or Ci i ring) on the basis of the ring size of the products. This presumably results from fixation of specific conformations of the intermediates on a hypothetical enzyme surface. The larger diversity of structure for sesquiterpenoids than for di- or tri-terpenoids could then reflect the larger conformational flexibility of a Cio or Cii ring (which are often involved in the formation of the former) than of the Ce rings that are usually implicated in the latter. 

The formation of halogenated sesquiterpenoids in Laurencia intricata has been the subject of speculation and the finding of a- and /3-snyderol (63) and (64) in several Laurencia species was held to support the involvement of a brominated monocyclofarnesol intermediate for chamigrane derivatives [c.g. elatol (65)]. The latter and caespitol (66) co-occur in L. obtusa and it was proposed that a bisabolonium ion (67) may be the common precursor for these two skeletal types. 

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