Browsing by Author "Fukuyama, Tohru"
Now showing 1 - 16 of 16
Results Per Page
Sort Options
Item A novel tin-mediated indole synthesis and its application to natural product synthesis(1996) Peng, Ge; Fukuyama, TohruA new indole synthesis is described. The key step involves a novel tin-mediated free radical reaction to generate unstable 2-tri-n-butylstannyl-3-substituted indoles, which upon mild acidic workup, furnishes 3-substituted indoles. The 2-tri-n-butylstannyl-3-substituted indoles are also subjected to a one-pot Stille coupling to provide 2,3-disubstituted indoles. Two applications of the above methodology are also described. The efficient total synthesis of (${\pm})$-vincadifformine involves the construction of the indole skeleton by using this indole formation reaction and a novel amine protection-deprotection procedure as crucial steps. A new synthetic approach is explored towards the total synthesis of antitumor agent discorhabdin C. The key step towards the key intermediate has greatly contributed to the development of the novel indole synthesis methodology.Item A stereocontrolled total synthesis of (+,-)-renieramycin A(1992) Linton, Steven Douglas; Fukuyama, TohruA novel synthetic route via iterative condensations of piperazinedione and substituted benzaldehydes has resulted in the first total synthesis of the complex antibiotic, renieramycin A 1a. Salient features include an acyliminium ion-mediated construction of a diazabicyclo (3.3.1) nonane nucleus, which allows for stereoselective hydrogenation and benzylic oxidation. The stereochemistry of the angelate side chain was unequivocally determined by X-ray crystallographic analysis of the penultimate intermediate, 67b. (DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)Item A total synthesis of (+,-)-quinocarcin(1988) Nunes, Joseph John; Fukuyama, TohruA synthetic route via the key intermediate DX-52-1 21 has resulted in the first total synthesis of the complex antitumor antibiotic quinocarcin 1. Salient features include an acyliminium ion-mediated stereoselective construction of a diazabicyclo (3.2.1) octane nucleus, a stereoselective Pictet-Spengler cyclization, and a silver assisted conversion of DX-52-1 to the title compound.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)Item Reactions of [Alpha]-Acyl-[Alpha] Diazoacetaldeydes(1980) Ananthanarayan, T. P.; Wenkert, Ernest; Lewis, Edward S.; Fukuyama, TohruThe copper-catalyzed thermolysis of ethyl diazoformylacetate and diazomalonaldehyde in n-butyl vinyl ether has been shown to produce ethyl 5-n-butoxy-4,5-dihydrofuran-3-carboxylate and 2-n-butoxy-2,3-dihydro-4-pyrone, respectively.Item Stereocontrolled total synthesis of (+/-)-gelsemine(1996) Liu, Gang; Fukuyama, TohruGelsemine (1) has been recognized as the major alkaloid component of Gelsemium sempervirens since 1870. It has attracted numerous synthetic efforts since the 1960s due to its unique rigid, hexacyclic cage structure. The first completely stereocontrolled total synthesis of gelsemine (1) via 21-oxogelsemine (3) is described herein. This synthesis features a stereospecific condensation between cyclopropyl carboxaldehyde (240) and 4-iodo-oxindole (259), facile construction of the tetracyclic intermediate (262) through a novel application of divinylcyclopropane-cycloheptadiene rearrangement, and an unprecedented silver-mediated cyclization between carbamoyl chloride and ene-carbamate.(UNFORMATTED TABLE OR EQUATION FOLLOWS)$$\vbox{\vskip108pt}$$(TABLE/EQUATION ENDS)Item Synthesis of optically pure mitomycin C: A new route to FR900482(1994) Linsell, Martin Sheringham; Fukuyama, TohruOptically pure mitomycin C was synthesized in 28 steps and 5% overall yield from 2,6-dimethoxytoluene. The route followed was a variation upon previous work in our laboratories and the asymmetry was achieved by the resolution of racemic mitomycin A, an advanced intermediate. Our efforts at finding a new route to an intermediate in the synthesis of FR900482, are also described here. The key step was the cyclization of an epoxy-acetamide under basic conditions to form an eight-membered lactam.Item Synthetic studies on ecteinascidin 743(1995) Jow, Chung-Kuang; Fukuyama, TohruSynthetic studies on ecteinascidin 743 (b), an antitumor antibiotic, are described. The key reactions include: (1) an acylimmium ion-mediated stereoselective construction of the optically pure diazobicyclo (3.3.1) nonane nucleus 6, (2) a stereocontrolled Pictet-Spengler cyclization for the formation of tetrahydroisoquinoline 2, and (3) the attempted benzylic oxidation of the pentacyclic phenol 22.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)Item Synthetic studies on naphthyridinomycin: A total synthesis of (+)-cyanocycline A(1989) Li, Leping; Fukuyama, TohruA synthetic route via chiral precursor 74* had led to a total synthesis of (+)-cyanocycline A. This optically pure synthesis unequivocally determined the absolute stereochemistry of natural cyanocycline A as 2, in contrast to a previously reported X-ray crystallographic assignment as presented on 2$\prime$. ftn*Please refer to dissertation for diagrams.Item Synthetic studies toward the total synthesis of (+)-anthramycin total syntheses of (+)-neothramycins A and B(1990) Lin, Shao-Cheng; Fukuyama, TohruThrough the serendipitous discovery of a palladium catalyzed conversion of ethylthiol esters to their corresponding aldehydes, the pyrrolo (1,4) benzodiazepine systems found in (+)-anthramycin 1a* and (+)-neothramycins A 2a and B 2b have been constructed from the diethylthiol esters 3 and 4 respectively. A key intermediate 5 for the total synthesis of (+)-anthramycin and a facile route to (+)-neothramycins A and B are thus provided. ftn*Please refer to dissertation for diagrams.Item Synthetic studies towards the total synthesis of discorhabdin C(1994) Li, Tangqing; Fukuyama, TohruTwo synthetic approaches towards the total synthesis of discorhabdin C (3) are described. The general strategy for construction of azacarbocyclic spiro dienone system is to employ an intramolecular para-phenolic alkylation (58 to 43). The key reaction for the first approach is a newly improved aromatic Claisen rearrangement. The key reaction for the second approach is a novel tin-mediated indole synthesis developed in our laboratory.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)Item Synthetic studies towards the total synthesis of renieramycin A (Antibiotics)(1988) Tun, Min Min; Fukuyama, TohruFormation of the skeleton of renieramycin A was achieved through sequential condensations of piperazinedione and substituted benzaldehydes. One of the key reactions of this synthesis, oxidation of benzylic position, produced hydroxylated compound 62 (see p. 22 in dissertation for illustration). Further elaboration of 62 has resulted in N-methyl 65 (p. 22), an important precursor to renieramycin A.Item Synthetic studies towards the total synthesis of the saframycins(1988) Ajeck-Carman, Karen Lynn; Fukuyama, TohruA key improvement to the original saframycin B synthesis involves efficient sequential piperazinedione condensations to yield a basic saframycin skeleton from which all congeners might be made. Approaches toward the total synthesis of saframycin A result in formation of two advanced intermediates. The first, a pentacyclic diphenol nitrile with at least four out of five stereocenters established, is synthesized via a multistep scheme which involves a Pictet-Spengler type phenolic cyclization. The second advanced intermediate is produced via a route which involves cleavage of an imidazolidine ring with concomitant introduction of cyanide. An isomer of saframycin A is synthesized using this approach.Item Total synthesis of (-)-hapalindole G: A novel tin-mediated indole synthesis(1994) Chen, Xiaoqi; Fukuyama, TohruThe first total synthesis of ($-$)-hapalindole G, a member of novel chlorine- and isonitrile-containing hapalindoles from the cultured cyanophyte Hapalosiphon fontinalis, is accomplished. Our 21-step synthesis of ($-$)-hapalindole G from ($-$)-carveol features a stereospecific introduction of chlorine next to a quaternary center via cleavage of the cyclopropane intermediate and facile elaboration of the indole moiety through a conjugate addition of lithium methyl methylthiomethyl sulfoxide to an enone followed by hydrolysis of the resultant adduct. The absolute configuration of ($-$)-hapalindole G has therefore been confirmed on the basis of the specific rotation of our synthetic sample. Also described herein is a novel tin-mediated radical indole synthesis by using o-isocyanostyrene derivatives as starting materials via 2-tri-n-butylstannyl-3-substituted indoles as intermediates. The 2-tri-n-butylstannyl-indoles were also subjected to the one-pot Stille coupling reaction and iodination. The iodoindoles were capable of further manipulation. Our efficient synthesis paves the way for a facile construction of a variety of 3- or 2,3-substituted indoles from readily accessible isonitriles.Item Total synthesis of (-)-safracin B total synthesis of (-)-thiangazole development of sulfonamide chemistry(1997) Cheung, Mui; Fukuyama, TohruChapter I describes the stereocontrolled total synthesis of ($-$)-safracin B with antibacterial and antitumor activities. The convergent approach for the synthesis of safracin B can be readily applied to the synthesis of the related isoquinolinequinone family such as saframycins and ecteinascidins. Chapter II discusses the total synthesis of ($-$)-thiangazole, a substance with potent anti-HIV-1 activity in vitro. An efficient synthetic pathway is developed to enable diverse modification of both ends of thiangazole and thus provide a rapid access to a variety of analogs. Chapter III outlines the development of new chemistry of nitrobenzenesulfonamides, N-Boc and N-Alloc nitrobenzene sulfonamides, and alkylsulfonamides for the efficient preparation of secondary amines and protected primary amines.Item Total synthesis of (-)-tantazole B. Total synthesis of (+,-)-FR900482(1993) Xu, Lianhong; Fukuyama, TohruTantazole B is a newly isolated tolytoxin. FR900482 is a recently isolated potent antitumor antibiotic. They both have novel structural features which present challenges to the synthetic chemists. The first total synthesis and structure revision of ($-$)-tantazole B is described herein. A convergent methodology is developed and could be applied to the synthesis of the other members of oxazole/thiazoline family.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI) The first and, to date, only total synthesis of $(\pm)$-FR900482 is also described here. The stereocontrolled total synthesis of FR900482 features a facile construction of the 8-membered intermediate through reductive amination, stereospecific hydroxymethyla-tion and efficient oxidation of the amine to the hydroxylamine.Item Total synthesis of mitomycins(1990) Yang, Lihu; Fukuyama, TohruThe total synthesis of mitomycins via isomitomycin A is described. Key reactions are a Michael-type coupling reaction between chalcone (94)* and 5-ethylthio-2-trimethylsiloxyfuran, followed by an azido-olefin cyclization. The first route took 30 steps from 2,6-dimethoxytoluene in a overall yield of 6%. The improved second route contains 26 steps with overall yield of 10% from the same staring material. Resolution of an synthetic intermediate resulted in both (+)- and ($-$)-isomitomycin A (15). X-ray crystallographic analysis of an intermediate with known chiral auxiliary which led to the natural ($-$)-isomitomycin A unequivocally determined the absolute stereochemistry of mitomycins. ftn*Please refer to dissertation for diagrams.