Biogenetic synthesis

Shimamura, T. et ah, Biogenetic synthesis of biflavonoids, lophirones B and C, from Lophira... 

There are many reports on the biogenetic synthesis of these alkaloids by phenol oxidation. These reactions were carried out using a diphenolic isoquinoline with one-electron oxidizing reagents ferric chloride, potassium ferricyanide, manganese dioxide, and so on. In order to obtain the androcymbine-type compound 82 the diphenolic isoquinoline 81 was subjected to phenol oxidation with potassium ferricyanide (3a) and with ferric chloride (2b), respectively, but instead the homo-aporphine 83 (2a) coupled at the ortho-ortho position to the hydroxy groups. 

The racemic laudanosine (7g) syntheses were referred to earlier in The Alkaloids (Vol. XII, p. 348). From the racemic mixture it is difficult to obtain (S)-(+)-laudanosine which is widely distributed in nature. The synthesis of its unnatural (R )-form (in poor yields) has been reported (asymmetric reduction of 3,4-dihydropapaverine with lithium butyl-(hydro)dipinan-3a-y borate) (363). Recently, a description of the biogenetic synthesis of these two forms from methyl-L-(+)-3,4-dihy-droxyphenylalaninate hydrochloride by condensation with sodium 3-(3,4-dimethoxyphenyl)glycinate at pH 4 and 35° was given. Thus, a dia-stereoisomeric mixture of the Pictet-Spengler products 11a and lib (ratio... 

Biogenetic synthesis of the aspidospermine skeleton requires the preparation of an intermediate with the skeleton of the Cio mevalonate-derived unit from which the aliphatic carbon skeleton of rings C and D is built and its subsequent condensation with tryptamine. Such a... 

A particularly interesting approach by Corey, Fleet and Kato [74] which resembles the biogenetic synthesis of prostaglandins, was achieved by means of the cyclisation of the epoxytrienamide (80) with boron trifiuoride etherate and then hydrolysis with potassium biphthalate to afford the lactone (76) and the corresponding C-OH epimer. 

Tsuge, O., Watanabe, H., and Kanemasa, S. (1984) Intramolecular oxidative coupling of brominated 2,42-dihydroxy-diarylmethanes. A biogenetic synthesis of thelepin and its analogs. Chem. Lett., 1415-1418. 

Review Problem 17 Design a synthesis for TM 206, an intermediate in Crandall and Lewton s biogenetically patterned synthesis of cedrene ( J. Amer. Chem. Soc.. 1969, 91, 2127). 

The synthetic process proceeding under physiological conditions can be imitated in vitro with the object of establishing the validity of biogenetic hypotheses (293) as well as finding new potential routes for the synthesis of pharmaceuticals (294). 

The latter, which is not normally isolated, may, under favorable conditions, be trapped in the presence of a strong nucleophile, as in the conversion of 340 into 338. It was surmised that the biogenetically modelled synthesis of strychnine-type systems was a demonstration of such a reaction. 

In contrast to the wealth of biogenetic speculation and model experimentation, none of which has direct bearing on actual biochemical events in the synthesis of /3-carbolines in their natural habitat, very few biosynthetic investigations have been carried out. As predicted, radioactivity from 2- C-tryptophan was incorporated into carbon atom-3 of the 1,2,3,4,4a,9a-hexahydro-)3-carboline moiety of ajmaUne and into carbon atom-3 of the jS-carbohnium segment... 

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. 

Marine sponges are a source of an array of polycyclic diamine alkaloids of common biogenetic origin. This class of secondary metabolites has been the subject of four previous reviews [4-7]. Therefore, the present review will include literature reports previously not discussed, dealing with the isolation, structure determination, biological activities, and total synthesis of polycycUc diamine alkaloids isolated from marine sponges. This review will not include guanidine alkaloids [8,9] or the manzamine alkaloids [10,11], since these compounds have been recently reviewed elsewhere. Only polycycUc... 

The biogenetic approach, which is a linear approach, is based on the stepwise disconnection of 18 into a series of biogenetically related alkaloid precursors. The precursors are usually built up in the actual synthesis with the C10 indole chromophore attached from the beginning and with stepwise modification of the alicyclic portion of the molecule later on. An example of this kind of approach is illustrated in Scheme 14 (43). 3(R)-Vobasinediol (58) is... 

The protoberberine alkaloids (5-75) play important roles as precursors in the biosynthesis of a variety of related isoquinoline alkaloids such as protopine, phthalideisoquinoline, spirobenzylisoquinoline, rhoeadine, inde-nobenzazepine, secoberbine, and benzo[c]phenanthridine alkaloids. Chemical transformations of protoberberines to these alkaloids are particularly interesting and exciting from the biogenetic viewpoint and further from ready availability of starting protoberberines in nature or synthesis. 

Secoquettamine (234) and dihydrosecoquettamine (235) together with their probable biogenetic precursor quettamine (236) form a small group of alkaloids. They were isolated by Shamma et at. (179) from Berberis baluchista-nica in yields of 0.00036,0.00017, and 0.0012%, respectively. These alkaloids incorporate either a benzofuran or a dihydrobenzofuran ring within the molecular framework, and the seco ones possess the /V,W-dimethylaminoethyl substituent. The structures of these bases were determined on the grounds of spectral data as well as by total synthesis. There is one chiral center at C in dihydrosecoquettamine (235) however, the base was isolated in the form of a racemic mixture (179). 

Recently, Mander and coworkers [122] reported the total synthesis of sordaricin (4-347), the aglycone of the potent antifungal diterpene sordarin which was first isolated in 1971 from the ascomycete Sordaria araneosa. Two approaches were explored the first method utilized a possible biogenetic Diels-Alder reaction the second was based on a domino retro-Diels-Alder/intramolecular Diels-Alder process. Thus, heating of 4-348 led, with extrusion of cyclopentadiene, to a 1,3-butadiene as intermediate which underwent an intramolecular Diels-Alder reaction to give the desired 4-349 as the main product, together with a small amount of 4-350 (Scheme 4.77). 

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