Shikimate-derived metabolites. 11. A total synthesis of (.+-.)-chorismic acid

Ganem, Bruce; Ikota, Nobuo; Muralidharan, Vimudha; Wade, Warren S.; Young, Stanley D.; Yukimoto, Yusuke

doi:10.1021/ja00388a055

Cited by 52 publications

(24 citation statements)

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“…Following the procedures developed by Ganem et al, 11 the alcohol 7 was converted into the 2-alkoxymalonate 9 on treatment with dimethyl diazomalonate 12 in the presence of a catalytic amount of rhodium() acetate, and alkylation using triethylamine and Eschenmoser's salt 13 ative elimination was then achieved by heating a solution of the amine 10 with an excess of methyl iodide in acetonitrile under reflux and gave the enol pyruvate 11 in a yield of 48% based on the alcohol 7. Cyclization of the vinylic bromide 11 was carried out by treatment with tributyltin hydride and a trace of azoisobutyronitrile in benzene-acetonitrile heated under reflux and gave the (E)-and (Z)-diesters 12 and 13, ratio 12 : 13 = 80 : 20, combined yield 40%.…”

Section: Resultsmentioning

confidence: 99%

“…Flash chromatography, eluting with light petroleum-ether (3 : 1) gave the cyclised products 35-37, for yields see Table 1. The (E)-isomer of the title compound 35 had the following data: ν max /cm Ϫ1 1758, 1617, 1481, 1429, 1258, 1175, 1126, 1075, 730 and 700; δ H 2.23 (1 H, m, 5-H eq ), 2.41 (1 H, br dt, J 5, 13, 5-H ax ), 2.63 (1 H, dd, J 10, 14, 3-H ax ), 2.83 (1 H, br dd, J 4, 14, 3-H eq ), 3.38 (1 H, dt, J 3, 11, 6-H ax ), 3.82 (3 H,s,OCH 3 ), 4.06 (1 H,ddd,J 4,5,11,4.12 (1 H,dd,J 4,10,5.98 (1 H,s,m,ArH); m/z (CI) 507 (M ϩ ϩ 1, 10%) and 429 (100). The (Z)-isomer of the title compound 36 had the following data: ν max /cm Ϫ1 1759, 1714, 1617, 1481, 1430, 1369, 1260, 1205, 1177, 1134, 1075, 730 and 700; δ H 2.39 (2 H, br m, 5-H 2 ), 2.67 (2 H, br m, 3-H 2 ), 3.55 (1 H, dt, J 3, 11, 6-H ax ), 3.58 (1 H,s,OCH 3 ), 3.82 (1 H, dd, J 4, 10, 2-H), 4.26 (1 H, ddd, J 4, 5, 11, 6-H eq ), 5.98 (1 H,s,m,ArH); m/z (CI) 507 (M ϩ ϩ 1, 6%) and 429 (100).…”

Section: (E)-and (Z)-2-methoxycarbonyl-4-(triphenylstannylmethylene)-mentioning

confidence: 99%

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An approach to the C(10)–C(16) fragment of the bryostatins: stereoselective exocyclic double-bond formation by vinyl radical cyclization

Maguire¹,

Munt²,

Thomas³

1998

J. Chem. Soc., Perkin Trans. 1

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On treatment with tributyltin hydride, the vinyl bromide 11 and the vinyl iodide 26 cyclize to give mixtures of the (E)-and (Z)-4-(alkoxycarbonylmethylene)tetrahydropyrans 12/13 and 27/28 in which the (E)-isomers 12 and 27 are the major components accounting for 80% of the products. Addition of triphenyltin hydride to the alkyne 34 similarly initiates cyclization giving a mixture of products 35-37, the composition of the mixture depending upon the concentration of the tin hydride. These results are consistent with faster cyclization of the (Z)-vinyl radical with kinetic formation of five-membered ring containing products which are either trapped by hydrogen transfer from the tin hydride or which rearrange to form a 4-methylenetetrahydropyran. This chemistry was applied to prepare the cis-2,6-disubstituted 4-(methoxycarbonylmethylene)tetrahydropyran 50 which may be useful for the introduction of the C(10)-C(16) fragment into the bryostatins. Cyclization of the p-methoxybenzyl protected vinyl iodide 58 is less stereoselective, perhaps because of intramolecular hydrogen transfer from the p-methoxybenzyl group.The bryostatins, e.g. bryostatin 7 1, comprise an important group of macrolides which are isolated from invertebrate filter feeders including Bugula neritina and which display potent antitumour activity. 1 The total synthesis of the bryostatins is of considerable interest at present because of the potential of these compounds as chemotherapeutic reagents with a need for a better understanding of their structure-activity relationships. To date one total synthesis of a bryostatin has been described 2 together with several reports of approaches to the synthesis of various fragments. 3-5

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Section: Resultsmentioning

confidence: 99%

Section: (E)-and (Z)-2-methoxycarbonyl-4-(triphenylstannylmethylene)-mentioning

confidence: 99%

An approach to the C(10)–C(16) fragment of the bryostatins: stereoselective exocyclic double-bond formation by vinyl radical cyclization

Maguire¹,

Munt²,

Thomas³

1998

J. Chem. Soc., Perkin Trans. 1

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“…25 Then treatment with MeI gave R-methylene ester 10 via elimination of an ammonium salt. 26 Michael addition of substituted thiophenol to methylene product 10 under basic conditions gave thioether derivatives 11a,b. The methyl ester of compounds 11a,b was reduced with DIBAL-H and NaBH 4 to give alcohols 12a,b, which were treated with NsNHBoc under Mitsunobu conditions 27 to provide Boc-protected Ns-amides 13a,b.…”

Section: Chemistrymentioning

confidence: 99%

Investigation of the Histamine H3 Receptor Binding Site. Design and Synthesis of Hybrid Agonists with a Lipophilic Side Chain

et al. 2010

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As a part of our search for novel histamine H3 receptor agonists, we designed and synthesized hybrid compounds in which the lipophilic (4'-alkylphenylthio)ethyl moiety of a novel H3 receptor agonist, 4-(2-(4'-tert-butylphenylthio)ethyl)-1H-imidazole (1), was incorporated into N(alpha)-methylhistamine, immepip, and immethridine derivatives. These hybrid compounds were expected to interact concurrently with the histamine-binding site and a putative hydrophobic region in the H3 receptor. Among them, piperidine- and pyridine-type derivatives displayed partial agonist activity, and (S)-4-(1-(1H-imidazol-4-yl)-2-(4-(trifluoromethyl)phenylthio)ethyl)piperidine (36) was identified as a potent H3 agonist. We performed computational docking studies to examine the binding mode of the agonists. The results indicated that immepip interacts with the key residues, Asp114 and Glu206, in a different manner from histamine. The binding mode of 36 to these residues is similar to that of immepip, and the lipophilic tail of 36 has an additional interaction with a hydrophobic region in transmembrane helix 6 of the receptor. These results indicated that 36 served as a useful tool for studies on receptor-agonist interactions and drug design.

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“…Alcohol 167 was then converted to the alkoxymalonate 169 by carbenoid insertion with 168 and rhodium acetate. 74 Alkylation of this malonate with Me 2 N=CH 2 ϩ I Ϫ 75 and decarboxylative elimination subsequently provided the enol enoate 171. A highly chemoselective stannylcupration 45 was now effected on alkynyl ester 171, despite the presence of the enol enoate, which also could have functioned as a possible Michael acceptor.…”

Section: Thomas' Synthetic Studies On Bryostatin 11 7273mentioning

confidence: 99%