Pinnaic acid and tauropinnaic acid: Two novel fatty acids composing a 6-azaspiro[4.5]decane unit from the Okinawan bivalve Pinna muricata

Chou, Tong; Kuramoto, Makoto; Otani, Yuko; Shikano, Mayumi; Yazawa, Kazunaga; Uemura, Daisuke

doi:10.1016/0040-4039(96)00704-6

Cited by 120 publications

(94 citation statements)

References 11 publications

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“…Halichlorine (1) [1] and the pinnaic acids (2a, 2b) [2], marine alkaloids recently isolated by Uemura and co-workers, exhibit considerable structural homology. Halichlorine was found to selectively inhibit the induced expression of VCAM-1 (Vascular Cell Adhesion Molecule-1) [3].…”

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confidence: 99%

“…Attempts to actually interconvert 11a and 11b via a retro-Michael reaction proved unsuccessful in our hands. The pinnaic acids themselves have been suggested to adopt a conformation similar to that of 11a [2]. It remains to be clarified whether inversion of the conformation at C(14) (i.e., upon passing from the halichlorine to the presumed pinnaic acid series [2]) is also influential in dictating the overall conformation of the aza-spirobicyclic core 1 ).…”

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confidence: 99%

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On the Conformations of Halichlorine and the Pinnaic Acids: Nitrogen Inversion as a Possible Determinant of Biological Profile

Trauner

Churchill

2000

HCA

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Dedicated to Professor Albert Eschenmoser on the occasion of his 75th birthday Although the marine alkaloids halichlorine (1) and the pinnaic acids 2, which contain a quinolizidine ring system, exhibit considerable structural homology, they act upon different biological targets (VCAM-1 and cPLA 2 , respectively). Quinolizidines can exist as cisoid or transoid invertomers. In the recently reported total synthesis of ()-halichlorine, it was determined by NMR that advanced intermediates 3 and 4, containing the spiroquinolizidine core, exhibit the transoid conformation, while the macrolactone-containing halichlorine has the cisoid conformation. We conclude that constraints imposed upon closure of the macrolactone ring force adoption of the cisoid conformation. The major conformational reorganization upon macrolactonization has implications for the design of pharmacophors and anticipated structure-activity relationships in their action on biological targets.Halichlorine (1) [1] and the pinnaic acids (2a, 2b) [2], marine alkaloids recently isolated by Uemura and co-workers, exhibit considerable structural homology. Halichlorine was found to selectively inhibit the induced expression of VCAM-1 (Vascular Cell Adhesion Molecule-1) [3]. By contrast, pinnaic acid and tauropinnaic acid were identified in an assay aimed at the identification of specific inhibitors of cytosolic phospholipase A 2 (cPLA 2 ). Since both VCAM-1 and cPLA 2 play key roles in the inflammatory cascade, such agents might be useful in the discovery and development of novel drugs against various diseases, including autoimmunity disorders and cancer. The value of such compounds as leads could be much enhanced through a clearer understanding of their solution conformations. In the course of our recent total synthesis of ()-halichlorine [4], we came upon several interesting findings in this regard. We noticed that crucial NMR-spectral features of a series of advanced intermediates incorporating the spiroquinolizidine framework (3a ± 3e, 4a ± 4b) bore little resemblance to those of halichlorine itself. In particular, the chemical shifts and the coupling patterns observed for the bridgehead H-atoms at C(5) (e.g., for compound 3a: d 2.37 ppm, dddd, J 3.6, 3.8, 10.5, 11.3 Hz) clearly differ from the corresponding ones found in halichlorine (d 3.18 ppm, dddd, J 1.5, 2.0, 6.5, 13.0 Hz) [1]. Since extensive NMR studies and an X-ray crystal structure of a subsequent derivative (vide infra) allowed us to unambiguously assign the configuration of our intermediate spiroquinolizidines 3 ± 4, a rationale for these strikingly different spectroscopic features was sought.Quinolizidines can exist as cisoid or transoid invertomers [5]. We propose that halichlorine adopts a cisoid conformation (see 5). This perception is at some variance

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On the Conformations of Halichlorine and the Pinnaic Acids: Nitrogen Inversion as a Possible Determinant of Biological Profile

Trauner

Churchill

2000

HCA

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“…由于在抗病毒、抗肿瘤、降血压、临床麻醉表现出广泛生物或药理活性 [3,4] , 已引起人们的极大关注. 随着人们对该类杂环化合物的深入研究和广泛应用, 发展和筛选具有新型结构和低毒高效药理活性的螺杂双环衍生物, 已成为氧杂或氮杂杂环化合物研究领域的热点.…”

Section: 3-二甲基-二苯基-24-氧杂-810-氮杂螺[55]十一unclassified

Efficient One-Pot Synthesis of 3,3-Dimethyl-diphenyl-2,4-dioxa-8,10-diazaspiro[5.5]undecane-1,5-dione-9-thione Derivatives

许招会¹,

周鹏²,

刘德永³

2016

Chin. J. Org. Chem.

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“…Many of these heterocycles have been found to play fundamental roles in biological processes and have exhibited important pharmacological activities. The appealing spiro architecture, often associated with significant biological activity, renders the spiro[pyrrolidine-3,3'-oxindole] alkaloids (Horsfiline, Rychnophylline, Elacomine) [2], spiro[piperidine-2',1-cycloalkane] frog neurotoxins (Histrionicotoxin 283A) [3] and marine products (Pinnaic acid) [4] or spiro[tetrahydroazepine-cyclohexene] shellfish toxins (Spirolides A-D) [5,6] interesting synthetic targets (Figure 1). …”

Section: Itroductionmentioning

confidence: 99%

“…The cyclization of these enynes was performed by a combination of 5 mol % of a cationic Pd (II) catalyst such as [(MeCN) 4 Pd](BF 4 ) 2 , 10 mol % of (S)-BINAP as a chiral bidentate PP-ligand, and 1 equiv of formic acid, in DMSO. It was reported that the reaction between fluorenyliden phthalides 90 and sodium azide in DMF gave the spiro compounds 91 in poor yields [112] (Scheme 37).…”

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confidence: 99%

Quinolines spiro annulated at heterocyclic fragment: Synthesis and properties

Kouznetsov

2005

Journal of Heterocyclic Chemistry

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Chemical information of the quinolines spiro annulated at heterocyclic fragment with cycloalkanes or heterocycles is reviewed. Synthetic approaches to three possible spiro-2(1H)-, spiro-3(4H)-and spiro-4(1H)quinoline core derivatives are analysed. Their syntheses are divided into three groups: a) chemical transformations of the substituted quinoline ring, b) construction of spiro structure from the alicyclic precursors, mainly, amine derivatives or imines preformed from cyclic ketones; c) rearrangements of more complex heterocycles leading to the spiro quinolines. Special attention is paid to spiro quinolines that display pharmacological properties. Synthetic routes to the discorhabdin alkaloids are also briefly discussed on in this review.

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Pinnaic acid and tauropinnaic acid: Two novel fatty acids composing a 6-azaspiro[4.5]decane unit from the Okinawan bivalve Pinna muricata

Cited by 120 publications

References 11 publications

On the Conformations of Halichlorine and the Pinnaic Acids: Nitrogen Inversion as a Possible Determinant of Biological Profile

On the Conformations of Halichlorine and the Pinnaic Acids: Nitrogen Inversion as a Possible Determinant of Biological Profile

Efficient One-Pot Synthesis of 3,3-Dimethyl-diphenyl-2,4-dioxa-8,10-diazaspiro[5.5]undecane-1,5-dione-9-thione Derivatives

Quinolines spiro annulated at heterocyclic fragment: Synthesis and properties

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