Cerebral Vasodilators

Cook, Paul; Im, James

doi:10.1056/nejm198112243052604

Cited by 46 publications

(1 citation statement)

References 14 publications

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“…Vincamine (sold under the trademark Oxybral-SR, Figure 12) is a peripheral vasodilator that increases blood flow to the brain can be used as a nootropic agent to combat the effects of aging. Vincamine is an indole alkaloid found in the Vinca minor and Catharanthus roseus [69]. Vincamine can be synthesized in the lab from related alkaloids [70].…”

Section: Indole Ring Containing Important Marketed Drug Moleculesmentioning

confidence: 99%

Biomedical Importance of Indoles

et al. 2013

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Section: Indole Ring Containing Important Marketed Drug Moleculesmentioning

confidence: 99%

Biomedical Importance of Indoles

et al. 2013

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Observations During Hypervolemic Hemodilution of Patients With Acute Focal Cerebral Ischemia

Wood¹

1982

JAMA

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Access to Electron‐Rich Arene‐Fused Hexahydroquinolizinones through a Gold‐Catalysis‐Initiated Cascade Process

Liu

Zhang

2012

Angewandte Chemie

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We have recently developed a two-step, one-pot synthesis of piperidine-4-ols. [1] In this reaction, the protonated cyclic imidate intermediate A, which is prepared by a gold-catalyzed [2] amide cyclization, is reduced by an external hydride (e.g., catecholborane), which initiates a key Ferrier rearrangement [3] (Scheme 1 a). We envisioned that a carbon nucleophile could replace the hydride in this chemistry; moreover, if such a nucleophile is attached to the amide nitrogen atom, addition of reagent in the course of the reaction is not needed. The reaction would constitute a goldcatalysis-initiated cascade process and might provide an efficient access to bicyclic piperidin-4-ones (e.g., 1, Scheme 1 b). Herein, we disclose our implementation of this strategy, which leads to an expedient synthesis of electronrich arene-fused hexahydroquinolizinones; its synthetic utility is illustrated by a succinct and stereoselective synthesis of dihydrocorynantheol without the use of any protecting group, and a formal synthesis of yohimbine and b-yohimbine.We chose tertiary formamide 1 a as substrate, as the formyl group would minimize steric hindrance for nucleophilic attack and the indole ring can act as a good neutral carbon nucleophile. Importantly, the anticipated product 2 a, a tetracyclic piperidine-4-one, shares a common hexahydro-indolo[2,3-a]quinolizine skeleton with various indole alkaloids, including dihydrocorynantheol, [4] yohimbine, [5] and vincamine [6] (Scheme 2). Notably, the latter two are marketed drugs for peripheral vasodilation. [7] The formamide 1 a was readily prepared from tryptamine through a straightforward two-step sequence: alkylation with but-3-yn-1-yl tosylate and formylation with ethyl formate. When 1 a was treated with IPrAuNTf 2 (5 mol %) at ambient temperature, desired product 2 a could not be detected (Table 1, entry 1). Instead, tricyclic formamide 3, which was formed by a gold-catalyzed 8-exo-dig cyclization, [8] was Scheme 1. A gold-catalysis-initiated cascade process toward bicyclic piperidine-4-ones.Scheme 2. Selected alkaloids containing the indolo[2,3-a]quinolizine skeleton. Table 1: Initial discovery and condition optimization. [a] EntryCatalyst Acid additive (equiv) Yield [%] [b]

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Cerebral Vasodilators

Cited by 46 publications

References 14 publications

Biomedical Importance of Indoles

Biomedical Importance of Indoles

Observations During Hypervolemic Hemodilution of Patients With Acute Focal Cerebral Ischemia

Access to Electron‐Rich Arene‐Fused Hexahydroquinolizinones through a Gold‐Catalysis‐Initiated Cascade Process

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