Biogenetic scheme

The biogenetic scheme for endiandric acids also predicts the plausible existence in nature of endiandric acids E (5), F (6), and G (7). Even though they are still undiscovered, their synthesis has been achieved (Scheme 6). For endiandric acids E and F, key intermediate 24 is converted, by conventional means, to aldehyde 35 via intermediate 34. Oxidation of 35 with silver oxide in the presence of sodium hydroxide results in the formation of endiandric acid E (5) in 90 % yield, whereas elaboration of the exo side chain by standard olefination (85 % yield) and alkaline hydrolysis (90 % yield) furnishes endiandric acid F (6). The construction of the remaining compound, endiandric acid G (7), commences with the methyl ester of endiandric acid D (36) and proceeds by partial reduction to the corresponding aldehyde, followed by olefination and hydrolysis with aqueous base as shown in Scheme 6. 

The intermediacy of a carbocation or complex-equivalent is attractive, if one considers that the nucleophilic ambident cyanide ion may be accomodated on secondary or tertiary cationic sites. Where exceptions (e.g., 125,126,134-136 cf. Sect. 4.3) exist, the cationic intermediate resides on a primary allylic carbon. The following skeletal types are examples of some biogenetic schemes offered in conjunction with the structural determination of isocyanoterpenoids ... 

Fig. I. (Left) Numbering of vinblastine-type alkaloids in this chapter according to the biogenetic scheme of LeMen and Taylor (134), with equivalent atoms in all synthetic intermediates equally labeled. (Right) Approximation of computer-generated, energy-minimized structure, obtained with the Clark Still MACROMODEL program.

The biosynthesis of monoterpenoids and camphor has been described by several authors (108-llU). Ruzicka (115,116) proposed a unified biogenetic scheme for terpenes. The biosynthetic building blocks for these terpenes are iso-prene units. The biosynthetically active isoprene units are isopentenyl pyrophosphate [l] and dimethyl allyl pyrophosphate [2] the compounds that are derived from acetate via mevalonic acid (Scheme V). Geranyl pyrophosphate [3] is the C-10 precursor for the terpenes (117). Banthorpe and Baxendale (ll8) confirmed the biosynthetic pathway of (iamphor via acetate mevalonate by conducting degradation study of camphor, biosynthesized from l c labelled mevalonic acid. The biosynthesis of camphor is summarised in Scheme VI. 

Several biogenetic schemes have been suggested to account for the origin of biphenyl and biphenyl ether lactonic alkaloids (52, 62, 83, 84). The proposals differ in the mode of biogenesis of the phenylquinolizidine moiety. Steps common to all the proposals are the reduction of oxo group in the phenylquinolizidone (130) followed by esterification with of / -coumaric acid (C6 C3) unit derived from phenylalanine via cinnamic acid. 

In light of the present evidence the biogenesis of metacyclophane Ly-thraceae alkaloids required revision, since the only published proposal (9) was based on pelletierine. A new biogenetic scheme was proposed which invoked intermediacy of A piperideine and two C6-C4 units [derived from /i-kctoester (193)]. An intermediate disubstituted piperidine (194) would give rise to two types of metacyclophane alkaloids as a result of reduction and phenol coupling as well as Michael addition in the case of the quinoli-zidine bases (10). 

A parallel biogenetic scheme has been suggested by Theuns et al. (24) for the formation of neodihydrothebaine (7) in Papaver bracteatum. In this case the route proceeds through the isomeric salutaridinol (103), which is derived by para-ortho coupling of reticuline (Scheme 29). It has been suggested that salutaridinol (103) (or thebaine) is the precursor of bractazonine (8), but in this case via a proerythrinadienone formed by aryl migration in the dienol-benzene rearrangement (24) (Scheme 30). 

No attempt as yet has been made to study the biogenesis of Buxus alkaloids. Indirect evidence gave rise to the presumption that in the biogenetic scheme lanosterol is followed by cycloartenol (or similar triterpene type). Goutarel (205) tentatively proposed a possible pathway via lanosterol, cycloartenol, 9j8,19-cyclo-4,4, 14a-trimethyI-5a-pregnan-3(8 - ol - 20 - one, 9, 19 - cyclo - 4,4, 14a - trimethyl - 5a - pregnan - 3,20 - dione, mono-, and diaminosteroids. 

The heart of these biosynthetic proposals is the oxidation of LXXXVIII to XCI, and the plausibility of this conversion has received dramatic support in two laboratories. In vitro oxidation of LXXXVIII (Ri = R2 = CH3) with alkaline ferricyanide was found by both Scott and coworkers 40) and by Mondon and Ehrhardt 40a) to afford XCI (Ri = R2 = CH3) in 35% yield. Mondon and Ehrhardt were then able to convert XCI to ( + )-dihydroerysodine, using the reactions shown in Fig. 12. This synthesis incidentally confirms the substitution pattern in ring D of erysodine. The facile formation of the erythrinane skeleton in this manner supports the basic biogenetic scheme, and the results of incorporation experiments with isotopically labelled LXXXVIII and XCI will be awaited with great interest. 

The joint occurrence of tylophorine and tylocrebrine with the seco-phenanthroindolizidine alkaloid septicine (XXI) in Ficus septica (4) lends support to the biogenetic scheme outlined above. It is also of interest that septicine is transformed to a mixture of tylophorine and tylocrebrine on UV-irradiation. It is quite possible that the amorphous base (mp 125°-130°), of Chopra et al. 10) is in fact septicine. 

Cn.m.r. analysis and limited chemical evidence. Of considerable interest to biosynthetic and synthetic chemists in this report is the proposal of a unified biogenetic scheme for both classes of alkaloid. Available evidence does not allow the formulation of a single biosynthetic pathway. 

Atropine was isolated by Mein in 1831 (58), and since then the synthesis of both atropine and scopolamine has been achieved (59,60). A biogenetic scheme for the synthesis of atro-pine-like alkaloids in datura species starting from ornithine has been described (61). 

These results, and consideration of Robinson s biogenetic scheme, lead to the alternative structures (6) or (14) for folicanthine. The ready mass spectral fragmentation of the alkaloid into two equal halves favours structure (6). ... 

An overall biogenetic scheme for the 3-alkylpiperidine alkaloids isolated from sponges in the order Haplosclerida. The numbers indicate molecular structures used as character states in the phylogenetic analysis based on molecule types presented in section 4.3. 

It has been shown that 7-deoxyloganic acid (81) is a precursor of various iridoglucosidesFeeding experiments on the plants Gardinia jasminoides and Paederia scandens have shown that the acid is incorporated into the irido-glucosides of these plants and a biogenetic scheme is proposed. ... 

With the absolute stereochemistry of (-f-)-a-ylangene (68, derived trisubstituted olefin) firmly established and a knowledge of the stereochemical inter-relationships, a biogenetic scheme encompassing all four classes of sesquiterpenes has been proposed. This is summarised in Scheme 1. The proposal envisages... 

Two almost simultaneous communications reported the successful syntheses of a-cedrene (123) and cedrol (124). Both syntheses were modelled along a proposed biogenetic scheme, and as such the penultimate goal was the generation of the cation (125) which should, and did, undergo a smooth acid-catalysed cyclisa-tion to a-cedrene. The two pathways to this cation differed in several respects yet practically coincided at the key spiro-dienone ester (126, R = Me and R = Et ). Whereas Crandall and Lawton completed the synthesis by formic acid treatment of the alcohol (127), Corey et al. found that similar treatment of the diol (128) also yielded a-cedrene, albeit in lower yield. Alternatively, the ene-diol (129) was converted into a-cedrene in better yield by formic acid treatment, thermolysis of the derived formates and subsequent lithium-ethylamine reduction of the diene (130). Finally, cedrol (124) was obtained by boron trifluoride cyclisation of the enol-acetate (131), followed by methyl-lithium treatment of the intermediate cedrone. 

Biogenetic schemes have been postulated to account for those sesquiterpenes which can be formally related to a eudesmane-type precursor via a 1,2-methyl migration (see Scheme 4). Thus, the skeletal and stereochemical features exhibited by the eremophilane-type (281) sesquiterpenes can be rationalised in terms of a precursor such as the cation (278), derivable from (277). By similar reasoning. 

There are relatively few sesquiterpenoids which cannot be derived from a farnesyl precursor either directly or indirectly. Recent examples of this rare group are furoventalene (403), the keto-lactone (404), the phenol (405), and the revised structure of humbertiol (406). Proposed biogenetic schemes for these compounds involve the combination of a C o monoterpene unit (either acyclic or cyclic) with a C5 unit (e.g., dimethylallyl pyrophosphate). 

In spite of the intriguing skeletal structure of the 8ecurinega alkaloids chemists have not yielded, with one exception 37), to the temptation of biogenetic speculation in the literature. Perhaps this speaks for the inability to write any one entirely convincing biogenetic scheme for this group or the increased awareness of the literature pollution problem. 

The biogenesis of this complex and highly oxygenated steroids (8 rings) containing a minimum of nine oxygen atoms calls for an elaborate system on the part of the plant. These were mainly formed in Physalis species, not in the other Solanaceous plants. A hypothetical biogenetic scheme, (Chart IV) was proposed by Crombie et al. . ... 

Hypothetic biogenetic scheme to withaphysalin C (114) to physalin C (191) by E. Glotter is shown in Chart VI. 

---