Stereoselective synthesis of (.+-.)-cyanocycline

Evans, David A.; Illig, Carl R.; Saddler, J. C.

doi:10.1021/ja00269a074

Cited by 46 publications

(15 citation statements)

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“…Treatment with trifluoroacetic acid led, presumably via 27, to the formation of rings A and E in a high yielding one pot procedure. 28 Reductive cleavage of the acetate protecting group and base-induced phenol-carbinol O-silyl migration furnished 39 as a single product. The amide was reduced under Birch conditions to the aminal, which was trapped by sodium cyanide to establish the characteristic nitrile function.…”

Section: Total Syntheses Of Cyanocycline Amentioning

confidence: 99%

“…In 1987, Evans and Illig performed a chiral switch of this synthesis by developing an asymmetric approach to a derivative of lactam 37 (Scheme 4). 28,29 Via an auxiliary based strategy, amino alcohol 40 was prepared in enantiomerically enriched form and added to racemic epoxy acid 41, a close analog of the previous intermediate 34. The diastereomeric amides were separated and the synthesis was carried on with Scheme 3 Evans' total synthesis of rac-cyanocycline A.…”

Section: Total Syntheses Of Cyanocycline Amentioning

confidence: 99%

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Recent progress in the total synthesis of naphthyridinomycin and lemonomycin tetrahydroisoquinoline antitumor antibiotics (TAAs)

2008

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In this tutorial review, which should be of general interest to synthetic organic chemists at large, recent progress in the total synthesis of the tetrahydroisoquinoline antitumor antibiotics cyanocycline A, naphthyridinomycin, bioxalomycin alpha2, and lemonomycin is highlighted in detail and some biological background information is given as well. Preparations of truncated derivatives and uncompleted synthetic approaches are also described. The literature coverage includes the newest research results through the year 2008.

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Section: Total Syntheses Of Cyanocycline Amentioning

confidence: 99%

Section: Total Syntheses Of Cyanocycline Amentioning

confidence: 99%

Recent progress in the total synthesis of naphthyridinomycin and lemonomycin tetrahydroisoquinoline antitumor antibiotics (TAAs)

2008

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“…14 Evans elegantly exploited this reaction as a starting point of the total synthesis of (AE)-cyanocycline A (26, Scheme 41.6), another tetrahydroisoquinoline antitumoral antibiotic that is produced by Streptomyces flavogriseus. 15,16 The natural product was obtained by the amidoalkylation between intermediates 27 and 28 followed by alkene-oxidative cleavage and Pictet-Spengler reaction with O-protected 2-aminoethanol 29.…”

Section: Isocyanatesmentioning

confidence: 99%

Cycloadditions with StereoselectiveCNBond Formation in Total Syntheses

Vincent

2013

Stereoselective Synthesis of Drugs and Natural Products

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Cycloadditions reactions are very efficient tools for the constructions of multiple bonds in one step and are therefore methods of choice for the total synthesis of natural products and drugs. The use of a terminal nitrogen containing partner allows for the stereoselective formations of a CN bond. Because of the vast number of nitrogen containing compounds available, this field has found a widespread interest in total synthesis. This chapter will cover the cycloadditions in which a CN bond is formed. It will be devoted to the description of [2+2], [3+2], [3+3], [4+2], and [2+2+2] processes that are key steps in total synthesis with imine, nitroso, azo, isocyanate, azomethine imine, azide, or azadiene reagents. A discussion of regioselectivity, diastereoselectivity, and enantioselectivity issues will be provided for each reaction.

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“…The azidation reaction with trisyl azide did not proceed cleanly for the 2-adamantyl analog 12 and we thus resorted to reaction of the anion of 12 with di-tert.butylazodicarboxylate (22) which proceeded satisfactorily giving the hydrazide 13. The remaining steps involved lithium hydroxide mediated hydrolysis of the…”

Section: Chemistrymentioning

confidence: 99%

Structure activity of C‐terminal modified analogs of Ac‐CCK‐7

Tilley

Danho

Shiuey

et al. 1992

International Journal of Peptide and Protein Research

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Previous work indicates that both the C‐terminal phenylalanine amide and the tryptophan moieties of chole‐cystokinin (CCK) are critical pharmacophores for interaction with either the A or B receptor subtypes. We have examined a series of analogs of Ac‐CCK‐7 [Ac‐Tyr(SO3H)‐Met‐Gly‐Trp‐Met‐Asp‐Phe33‐NH2] (2) in which the phenyl ring of the C‐terminal Phe‐NH2 has been modified. Compounds were assessed in binding assays using homogenated rat pancreatic membranes and bovine striatum as the source of CCK‐A and CCK‐B receptors respectively and for anorectic activity after intraperitoneal administration to rats. Substitution of a number of cycloalkyi or bicyclic aryl moieties for the phenyl ring of phenylalanine33 including cyclopentyl (20), cyclohexyl (21), cyclooctyl (23), 2‐(5,6,7,8‐tetrahydro)naphthyl (26), 2‐naphthyl (27), and 1‐naphthyl (29) led to analogs with 10–70 times the anorectic potency of 2. The anorectic activity of 21 was blocked by the specific CCK‐A receptor antagonist MK‐329. Other bulky aliphatic groups in place of the phenylalanine33 aromatic ring such as isopropyl, 2‐adamantyl and cyclohexylmethyl gave derivatives similar to 2 in potency. While most of the new compounds were comparable to CCK in binding assays, 23, 26, 27 and 29 were exceptionally potent with IC50s 10‐11‐10‐14 M in the pancreas. Compounds 23 and 29 were further evaluated for their ability to stimulate amylase secretion and found to have potencies similar to that of CCK. The dissociation between potency in the binding and amylase secretion assays suggests that they may interact with a high affinity binding site which is not coupled to amylase secretion. We conclude that CCK receptors possess a generous hydrophobic pocket capable of accommodating large alkyl groups in place of the side chain of phenylalanine33 and that the pharmacological profile of CCK analogs can be tailored by appropriate exploitation of this finding.

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Stereoselective synthesis of (.+-.)-cyanocycline

Cited by 46 publications

References 0 publications

Recent progress in the total synthesis of naphthyridinomycin and lemonomycin tetrahydroisoquinoline antitumor antibiotics (TAAs)

Recent progress in the total synthesis of naphthyridinomycin and lemonomycin tetrahydroisoquinoline antitumor antibiotics (TAAs)

Cycloadditions with StereoselectiveCNBond Formation in Total Syntheses

Structure activity of C‐terminal modified analogs of Ac‐CCK‐7

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