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Showing papers on "Total synthesis published in 1977"




Journal ArticleDOI
TL;DR: In this paper, the key intermediates, methyl alpha-L- and alpha-D-glucopyranosides, were obtained in seven steps from the ester without change of configuration of the asymmetric center, which became C-5 in the sugar molecule.

99 citations


Journal ArticleDOI
TL;DR: The available evidence indicates that the ease of formation of the disulfide bond A7–B7 does not depend on the precursor molecule already having an insulin-like conformation.
Abstract: Total synthesis of human insulin. IV. Description of the final steps. Recently a preliminary account was given of a new synthetic pathway leading to human insulin. In the present report the last steps of this synthesis – i.e. as from the unsymmetrical cystine derivative I – are described in detail. I contains the sequences A(14–21) and B(17–30), linked by the disulfide bridge A20-B19. These last steps are: (1) selective removal by pH-controlled acidolysis in trifluoroethanol of N(α)-Trt from leucine B17, (2) completion of the B-chain by coupling with the fragment B(1–16), (3) selective removal by trifluoroethanol of N(α)-Bpoc at tyrosine A14, (4) completion of the A-chain by coupling with the cyclic fragment A(1–13), (5) removal of the acid labile protecting groups, and (6) formation of the disulfide bond A7–B7 from the two S-acetamido-protected cysteine residues by treatment with iodine. As judged by the composition of the reaction mixture the closure of the 85-membered ring proceeds with a cyclization yield of over 70%. From the last step in the synthesis two products were obtained after extensive purification by counter-current distribution: pure human insulin in a yield of 50% and its [D-tyrosine B16]Isomer in a yield of 25%. Although the partial racemization of tyrosine B16 occurred during coupling with sequence B(1–16), the [D-tyrosine B 16]-stereoisomer could only be separated at the endproduct stage. The available evidence indicates that the ease of formation of the disulfide bond A7–B7 does not depend on the precursor molecule already having an insulin-like conformation.

93 citations



Journal ArticleDOI
TL;DR: In this article, a stereospecific, total synthesis of crystalline thromboxane B2 from D-glucose is described, and the synthesis is shown to be stable.
Abstract: A stereospecific, total synthesis of crystalline thromboxane B2 from D-glucose is described.

77 citations



Journal ArticleDOI
TL;DR: In this paper, a stereoselective total synthesis of the /3-methylene-y-lactone sesquiterpene, bakkenolide-A, is reported.
Abstract: A stereoselective total synthesis of the /3-methylene-y-lactone sesquiterpene, bakkenolide-A, is reported. The use of [2,3]-sigmatropic rearrangements within the context of constructing asymmetric quaternary centers has been explored. It has been found that steric factors appear to play a significant role in defining the levels of stereoselectivity observed in this class of molecular rearrangements. As a general reaction type, [2,3]-sigmatropic rearrangements constitute an exceptionally versatile class of bond reorganization processes which have many obvious applications in organic synthesis. Over the last decade such rearrangements have been widely studied, and the generality of the basic process illustrated in eq 1 has been established by numerous in-

68 citations


Journal ArticleDOI
TL;DR: Ddl-Pumiliotoxin-C was synthesized in a practical manner from trans-4-hexenal in a highly stereoselective fashion.
Abstract: dl-Pumiliotoxin-C (4) was synthesized in a practical manner from trans-4-hexenal (9). The key step 14 15 (Scheme 3) involves an intramolecular Diels-Alder reaction giving mainly the cis-fused indanols 15a, which were converted to the cis-fused ketone 16. After Beckmann-rearrangement of 16 the octahydroquinolinone 7 was transformed to the lactim-ether 23. (Scheme 7). Reaction of 23 with propylmagnesium bromide followed by hydrogenation furnished dl-4 in a highly stereoselective fashion.

62 citations



Journal ArticleDOI
TL;DR: The 'H NMR spectra of 3 and 4 are consistent with the assigned stereochemistry: 3 (CCI4, TMS), 6 7.1 (br s, 5 H), 6.3 (d, J = 12, 1 H), 5.5 (c)
Abstract: Rossi and J. F. Bunnett, ibid., 38, 3020 (1973); (c) J. V. Hay, T. Hudlicky, and J. F. Wolfe, J. Am. Chem. Soc., 97, 374 (1975): (d) M. F. Semmelhack, B. P. Chong, R. D. Stauffer, T. D. Rogerson, A. Chong, and L. D. Jones, ibid., 97, 2507 (1975). (3) The 'H NMR spectra of 3 and 4 are consistent with the assigned stereochemistry: 3 (CCI4, TMS), 6 7.1 (br s, 5 H), 6.3 (d, J = 12, 1 H), 5.5 (d, J =

Journal ArticleDOI
TL;DR: In this paper, a saturated cephalosporin analog 7-β-phenoxyacet-amido-3-ethoxy-O-2-isocepham-4-α-carboxylic acid 30, is described.
Abstract: The preparation by total synthesis of a saturated cephalosporin analog 7-β-phenoxyacet-amido-3-ethoxy-O-2-isocepham-4-α-carboxylic acid 30, is described. Compound 30 was prepared via cycloaddition of azidoacetyl chloride to the cinnamylidene Schiff base of ethyl 2-amino-3, 3-diethoxypropionate 13b to give the cis-3-azido-4-styryl β-lactam 15b. Ozonolysis of 15b followed by sodium borohydride reduction gave the alcohol 18b. Boron trifluoride treatment of 18b gave ethyl 7-β-azido-3- β-ethoxy-O-2-isocephem-4-carboxylate 27. Reduction of the azido group followed by coupling with phenoxyacetic acid and saponification of the ester gave 30. The mechanism of the cycloaddition reaction and the stereochemical assignments are also discussed.




Journal ArticleDOI
TL;DR: Natural Vincamine (1) has been synthesized in an enantioselective manner starting from the ethylpentenal 7 using a mixture of the diastereoisomeric racemates directly obtained from the silyl enol ether 11 and the dihydro-β-carboline 12.
Abstract: Natural Vincamine (1) has been synthesized in an enantioselective manner starting from the ethylpentenal 7. In the key step a mixture of the diastereoisomeric racemates, 14 and 15, was directly obtained from the silyl enol ether 11 and the dihydro-β-carboline 12 by the way of an intramolecular Mannich reaction of the intermediate 13(Scheme 4). The undesired stereoisomers, 14 and 15b, were recycled to 15a using the related reversible Mannich reaction 18 ⇄ 14 + 15, followed by crystallization of the salt from 15a and (+)malic acid. 15a was converted to natural vincamine (1) in several steps including the known transformation 20→1.

Journal ArticleDOI
TL;DR: In this article, the stereochemistry of the photoaddition of allene to hydroindenal was explored and proved by conversion into steviol methyl ester and isosteviolmethyl ester.


Journal ArticleDOI
TL;DR: The total synthesis of the perhydrohistrionicotoxin intermediate 23 was achieved in 25% overall-yield and represents a novel method for stereospecific and position-specific introduction of a nucleophilic butyl equivalent in α-position to a ketonic carbonyl group.
Abstract: Starting from ethyl 2-cyclohexen-1-carboxylate (3) the total synthesis of the perhydrohistrionicotoxin intermediate 23 was achieved in 25% overall-yield. The two key steps involve a positionally specific addition of HOBr to the oxime-olefin 7 and the alkylation of bromooxime 17 with 1-lithio-1-butyne. The latter represents a novel method for stereospecific and position-specific introduction of a nucleophilic butyl equivalent in α-position to a ketonic carbonyl group.

Journal ArticleDOI
TL;DR: The first biogenetic-type asymmetric synthesis of natural (+)-maritidine from L-tyrosine is described in this paper, where an asymmetric cyclization of dienone was found highly selectively to give one diastereomer preferentially.
Abstract: A first biogenetic-type asymmetric synthesis of natural (+)-maritidine from L-tyrosine is described. Phenolic oxidative coupline of monophenol (10b) with thallium (III) trifluoroacetate afforded the corresponding spiro dienone (11b) in 66.5% yield. Asymmetric cyclization of dienone (14) was found to occur highly selectively to give one diastereomer (15) preferentially. Removal of the carboxamide group in 15 was effected by reductive decyanization of the intermediate amino nitrile (18) by sodium in liquid ammonia to (+)-epimaritidine (19), which was epimerized to the objective (+)-maritidine by the known method.

Journal ArticleDOI
TL;DR: In this article, the first total synthesis of (±)-N,O-diacetylcylindrocarpinol 49, (±)cylindrocarine 51, (µ)-cylindricarpidine 1, and (ð)-cyclindricarine 52, starting from pent-4-enal and proceeding via the ketones 12 and 40, is described.



Journal ArticleDOI
TL;DR: A synthetic route to the antileukaemic lignan (±)-steganacin is described from the readily available piperonal and 3,4,5-trimethoxyphenylacetic acid.
Abstract: A synthetic route to the antileukaemic lignan (±)-steganacin (1) is described from the readily available piperonal and 3,4,5-trimethoxyphenylacetic acid. Diastereoisomerism encountered in a number of precursors has been ascribed unambiguously to the presence of the bridged biphenyl system (atropisomerism).

Journal ArticleDOI
TL;DR: The macrolide aglycon, erythronolide A, which has 10 asymmetric carbon atoms, substituted with hydroxyl and C-methyl groups can be considered as two functionalized acyclic segments bridged by a two-carbon unit (C-7-C-8) bearing a C- methyl group.
Abstract: Carbohydrates provide useful starting materials for the synthesis of polyfunctional, chiral natural products. The complex macrolide aglycon, erythronolide A, which has 10 asymmetric carbon atoms, substituted with hydroxyl and C-methyl groups can be considered as two functionalized acyclic segments (C-1—C-6 and C-9—C-15), bridged by a two-carbon unit (C-7 —C-8) bearing a C-methyl group. Approaches to the synthesis of these two segments from D -glucose are described, based on the systematic, stereocontrolled introduction of functional groups, and the efficient utilization of common synthetic intermediates.


Journal ArticleDOI
TL;DR: In this article, experimental details of the synthesis of 11β-methyl and 11beta-ethylestradiol by addition of Grignard reagents to 11-oxo-9alpha and 9beta-estratrienes are reported.