Biogenetic type synthesis

Schwartz MA, Holton RA (1970) Intramolecular oxidative phenol coupling. II. Biogenetic-type synthesis of (+-)-maritidine. J Am Chem Soc 92 1090-1092... 

Mannich reactions, or a close mechanistic analog, are important in the biosynthesis of many nitrogen-containing natural products. As a result, the Mannich reaction has played an important role in the synthesis of such compounds, especially in syntheses patterned after the mode of biosynthesis, i.e., biogenetic-type synthesis. The earliest example of the use of the Mannich reaction in this way was the successful synthesis of tropinone, a derivative of the alkaloid tropine, by Sir Robert Robinson in 1917. 

The full paper of Tietze s biogenetic-type synthesis of secologanin aglucone methyl ether and sweroside aglucone methyl ether has been published (Vol. 5, p. 18), and a second paper independently reports in full the rapid enzymic cleavage of secologanin to the bicyclic hemiacetal previously described by R. T. Brown (Vol. 7, p. 27) longer reaction times result in the formation of (146). ... 

The synthesis of camphor (80% optical purity) by heating optically pure di-hydrocarvone at 400 °C for 20 h is reminiscent of Money s racemic camphor synthesis (Vol. 1, p. 39) in that both correspond to a biogenetic-type synthesis via enol formation. Further synthetic work on deuteriated camphors (see references therein and Vol. 3, p. 67 Vol. 4, p. 48 Vol. 7, p. 38 for earlier work) includes syntheses of optically pure [8- Hi]-, [8- H2]-, and [8- H3]-(—)-camphor (204) by modification of known reactions (Scheme 5) and the use of an improved Zn-Cu... 

A biogenetic-type synthesis of the bicyclic penicillin-cephalosporin antibiotics from an acyclic tripeptide equivalent involves a double cyclization of compound (383) to form both the thiazoline and the /3-lactam rings in one step (384 Scheme 235) (75JA5008). 

Watanabe, T., Katayama, S., Nakashita, Y., and Yamauchi.M., Rcgio,specific(biogenetic-type) synthesis of 2-methyl-51I-pyrano 3,2-cl[l benzopyran-4-one, the basic skeleton in citromycetin, J. Chem. Soc. Chem. Commun., 761, 1981. 

The method has been used in biogenetic-type synthesis of di- and triterpenes it has also been used in the synthesis of Cecropia juvenile hormone. ... 

Quite often the type of compound isolated from Aplysia species depends on the location from which they were collected, and therefore, on the algae upon which they feed. A. kurodai collected from Mei Prefecture of Japan was found to contain an extended diterpene (with a prenylated eudismane skeleton)-aplysiadiol [13] and its methyl derivative [14] (29). It could safely be assumed that a brown alga on which this prosobranch feeds was the actual source of aplysiadiol. Recently a biogenetic type synthesis of 14 has been reported (30). 

Starting from (Z)-undeca-l,5-dien-3-ol a biogenetic-type synthesis of (+ )-dictyopterene A was achieved using the homoallyl-cyclopropyl rearrangement as the key step for cyclopropyl formation. Solvolysis of (Z)-3-mesyloxyundeca-l,5-diene under a variety of conditions failed to give cyclopropylmethyl compounds due to the presence of the terminal double bond. In contrast, (Z)-3-mesyloxy-l-(phenylthio)undeca-5-ene (3) afforded a mixture of epimeric cyclopropyl-methanols 4 in 91 % yield. Appropriate functional group transformation eventually leads to the desired dictyopterene A. 

Use of vanadium oxytrichloride for this type of oxidation results in much improved yields4 and provides the key step in a biogenetic-type synthesis of the Amaryllidaceae alkaloid ( )-maritidine (10). The starting material is O-methyl-... 

Bicyclo[2,2,l]heptanes.—The most interesting synthetic contribution to this area of monoterpenes is probably the biogenetic-type synthesis of camphor (222) by Money et a/. (- -)-Dihydrocarvone (219) is converted into a mixture of its enol acetates (220) and (221) and treatment of one of these [(220)] with boron trifluoride in methylene chloride yields camphor (222) in high yield however, it is racemic. The other enol acetate (221) gives carvenone (102) under these conditions. 

C(14) or C(10)-to-nitrogen bonding arrangement. The position of the acetoxy-group in (316 R = Ac) and thus the hydroxy-group in cancentrine was determined by examination of their n.m.r. spectra and by n.o.e. measurements. Cancentrine is a unique dimeric alkaloid constructed from morphine and cularine subunits and represents a formidable challenge for biogenetic-type synthesis. 

The full paper (Vol. 8, p. 58) on the biogenetic-type synthesis of the linalyl oxides has been published and dihydro-ocimenoyl oxide (230) has been synthesized by the regiospecific reaction of 2-methylbutanal with the y-carbon atom of a,a-dimethylallyltrimethylsilane catalysed by TiCU, presumably via cyclization of the corresponding y-chloro-alcohol. ° Straightforward syntheses of perillene (231 X = H,H) and egomaketone (231 X = O) involve prenylation... 

Attempts to devise a biogenetic-type synthesis of hirsutene (314) and derivatives cf. Vol. 7, pp. 79,80) have recently culminated in the successful conversion of protoilludane epoxide (315) into hirsUten-8a-ol (316) and compounds (317)— (319). In contrast the diastereomeric epoxide (320) under the same conditions (Bp3,Et20) provides the ketone (318) as the only product (Scheme 30). 

An interesting example of asymmetric induction has been utilized in a new biogenetic-type synthesis of (—)-tetrahydroharman and ( — )-1,2,3,4,6,7,12,12b-octahydroindoIo[2,3-a]quinolizine (6) from L-tryptophan the synthesis of (6) is outlined in Scheme 3. Apparently the Pictet-Spengler closure is stereospecific, and affords the 1,3-cis stereoisomer (6a) removal of the unwanted chiral centre is achieved in good yield and without epimerization at C-1 by NaBH4 reduction of an a-aminonitrile. This synthesis may well find application in other areas. The alkaloid (6) has also been synthesized by a more conventional, non-stereospecific route. ... 

Tabersonine (28), another /J-anilinoacrylate derivative, has been postulated to be a key biosynthetic precursor of all the Aspidosperma alkaloids and possibly also the iboga alkaloids. It is therefore a key compound for synthetic endeavors, but any potential synthesis of tabersonine poses an interesting problem because of the 14,15-double bond. Thus a biogenetic-type synthesis would involve the acrylic ester 478, the very ester postulated as the biosynthetic precursor of the Aspidosperma and iboga alkaloids. To date, efforts to produce this highly reactive ester have failed. 

A general method for the preparation of piperid-3-ols has been adapted to the biogenetic-type synthesis of pseudoconhydrine (40) (Scheme 3). Of the two... 

This ring contraction was used in a biogenetic-type synthesis of illudadiene (6) from 5. 

A three-step biogenetic-type synthesis of bioactive natural product Luotonin F174 (99H(51)1883) in 38% overall 3deld starts from the natural product pegamine 171 via PCC-oxidation, Friedlander condensation of 172, and chromium trioxide-periodic acid oxidation of 173 (Scheme 34) (02S323). 

In a biogenetic-type synthesis of humulene the 7r-allylpalladium complex (164), derived from the acetate (163), has been observed to cyclize intramolecularly in a highly stereoselective fashion, producing the cycloundecadienone (165)/° No detectable amounts of the positional isomer (nine-membered ring) or stereoisomers about the double bonds were observed. 

Douglas JL, Money T (1967) Tyrone studies-II. Biogenetic-type synthesis of phenolic compounds. Tetrahedron 23 3545-3555... 

Griffin DA, Staunton J (1975) A novel biogenetic-type synthesis of an orsellinic acid derivative. Chem Commun 675-676... 

Bhakuni DS 1984 Biosynthesis, aberrant biosynthesis and biogenetic type synthesis of some alkaloids of Indian medicinal plants. Proc Fifth Asian Symp Med Plants Spices, Aug 5. Nat Prod Res Inst, Seoul Natl Univ, Seoul, Korea, pp. 509-518... 

The biogenetic-type synthesis of a number of naturally occurring penta-cyclic triterpenoids and steroids from acyclic olefinic epoxide precursors has been achieved. Thus the epoxide (501) is transformed into dl-d-amynn (502) (8%) by SnCl4-MeN02 at 0 °C. ... 

Hay and Harris 153,157) have reported a biogenetic-type synthesis of lichexanthone (Scheme 14). To circumvent problems arising from numerous cyclisation pathways of a long polyketide chain these workers chose a starting compound with a pre-formed aromatic ring (132). Claisen condensation of the polyketide side chain of (132) in aqueous potassium hydroxide yielded a mixture of the benzophenone (133) and 3-0-methylnorlichexanthone (134). The benzophenone (133) could be converted into (134) by treatment with methanolic potassium hydroxide. Subsequent O-methylation of (134) with diazomethane yielded lichexanthone (135). 

A convenient high yield synthesis of 3-iodo-3-methylcephams (373) and 3-alkoxy-3-methylcephams is by reaction of the thiazoline azetidinone (372) with iodine or sulphenyi halides. Cooper first reported that (374), a degradation product of penicillin, gave a mixture of penicillin sulphoxide (376) and desacet-oxycephalosporin sulphoxide (377) when treated with /w-chloroperoxybenzoic acid in the presence of TFA, and this transformation was used in Kishi s biogenetic-type synthesis of penam and cephem derivatives- The results are not always... 

Nakatsuka, S., H. Tanino, and Y. Kism Biogenetic-Type Synthesis of Penicillin-Cephalosporin Antibiotics. I. A Stereocontrolled Synthesis of the Penam- and Cephem-Ring Systems from an Acyclic Tripeptide Equivalent. J. Amer. Chem. Soc. 97, 5008 (1975). 

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