Total Synthesis Guided Structure Elucidation of (+)‐Psychotetramine

Foo, Klement; Newhouse, Timothy R.; Mori, Ikue; Takayama, Hiromitsu; Baran, Phil S.

doi:10.1002/anie.201008048

Cited by 121 publications

(51 citation statements)

References 43 publications

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“…The distinctive chemical constituents of this genus are rich in polyindole, monoterpenoid indole, and isoquinoline alkaloids. Due to their fascinating structural complexity and biological significance, those alkaloids have attracted attention of both synthetic chemists and pharmacologists [2][3][4][5][6][7][8]. Some plants of this genus have been used in folk medicine for the treatment of constipation in Malaysia and China for a long period time.…”

Section: Introductionmentioning

confidence: 99%

Absolute configuration study of a new dimeric indole alkaloid from the leaves and twigs of Psychotria henryi

Liu

Wang

et al. 2013

Journal of Asian Natural Products Research

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Section: Introductionmentioning

confidence: 99%

Absolute configuration study of a new dimeric indole alkaloid from the leaves and twigs of Psychotria henryi

Liu

Wang

et al. 2013

Journal of Asian Natural Products Research

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“…For example, Baran's elegant synthesis of (+)-kapakahine B necessitated prolonged reaction times (24 h) and increased catalyst loadings (20 mol %) under Larock's standard conditions (Scheme 1A). 5c Similarly, Boger's landmark synthesis of the chloropeptins, which employed an intramolecular Larock macrocyclization of an aryl bromide, required excess [Pd] and dtbpf (1.1 and 1.3 equiv, respectively) to effect high yields (Scheme 1B). 6a …”

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confidence: 99%

A Mild and General Larock Indolization Protocol for the Preparation of Unnatural Tryptophans

2016

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A mild and general protocol for the Pd(0)-catalyzed heteroannulation of o-bromoanilines and alkynes is described. Application of a Pd(0)/P( t Bu) 3 catalyst system enables the efficient coupling of o-bromoanilines at 60 °C, mitigating deleterious side reactions and enabling access to a broad range of useful unnatural tryptophans. The utility of this new protocol is demonstrated in the highly convergent total synthesis of the bisindole natural product (−)-aspergilazine A. Graphical abstractThe development of new methods to prepare unnatural tryptophan derivatives is an important endeavor with interdisciplinary applications. In the context of natural product synthesis, a large number of alkaloids contain tryptophan subunits embedded explicitly or implicitly within their structures; 1 in chemical biology, functionalized tryptophan derivatives have emerged as important molecules for studying protein function and dynamics. 2 Although subtle perturbations to this core amino acid may seem trivial, the preparation of the requisite tryptophan building block often constitutes a substantial synthetic undertaking. The Pd-catalyzed heteroannulation reaction between o-bromoanilines and serine-derived alkynes represents a convergent approach to unnatural tryptophan derivatives; yet, its versatility has thus far been limited due to challenges of reactivity and functional group tolerance. Herein, we describe the development and application of a Pd-catalyzed synthesis of structurally complex and synthetically useful tryptophan derivatives from widely-* Corresponding Author: reisman@caltech.edu. Supporting Information: The Supporting Information is available free of charge on the ACS Publications website. Experimental data, characterization information, and spectra (PDF) commonly known as the Larock indole synthesis, is a powerful method for the preparation of 2,3-disubstituted indoles. 4,5,6 Larock's original conditions, which employ a "ligand-less" Pd-catalyst in conjunction with an inorganic base and chloride salt additive, were developed for o-iodoanilines and remain the most widely utilized ( Figure 1A). 7 In 2004, Senanayake and co-workers expanded the scope of this transformation to include o-chloro-and obromoanilines by employing a bidentate phosphine ligand, 1,1′-bis-di-tertbutylphosphinoferrocene (dtbpf), at elevated temperatures (110-130 °C), providing simple indoles in good yield and high regioselectivity (not shown). 8 HHS Public AccessDespite these advances, efforts to employ the Larock indole synthesis in complex settings, particularly using alkynyl substrates containing peptide functionality and o-bromoanilines, reveal significant limitations in the state of the art. For example, Baran's elegant synthesis of (+)-kapakahine B necessitated prolonged reaction times (24 h) and increased catalyst loadings (20 mol %) under Larock's standard conditions (Scheme 1A). 5c Similarly, Boger's landmark synthesis of the chloropeptins, which employed an intramolecular Larock macrocyclization of an aryl bromide, required e...

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“…[9] Densely functionalized natural products were decarboxylated in high yields; [17] indole (13), hydroxy (15, 18 a,and 19 a), ketones (17 and 19 a), and olefins (18 a and 19 a)were left unscathed. [19] Substrate 14,t hough not natural product-derived per se,s howcases the viability of this methodology to synthesize these alkaloids in ah ighly practical fashion. [18] Although 19 a can be furnished in good yields through PET-mediated decarboxylation, long reaction times (24 h), an expensive solvent (TFE), and Fukuzumisp hotosensitizer (more expensive than the starting carboxylic acid) are required.…”

Section: Sirmentioning

confidence: 99%

Nickel‐Catalyzed Barton Decarboxylation and Giese Reactions: A Practical Take on Classic Transforms

et al. 2016

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Tw on amed reactions of fundamental importance and paramount utility in organic synthesis have been reinvestigated, the Barton decarboxylation and Giese radical conjugate addition. N-hydroxyphthalimide (NHPI) based redox-active esters were found to be convenient starting materials for simple,t hermal, Ni-catalyzed radical formation and subsequent trapping with either ah ydrogen atom source (PhSiH 3 )o ra ne lectron-deficient olefin. These reactions feature operational simplicity,i nexpensive reagents,a nd enhanced scope as evidenced by examples in the realm of peptide chemistry.

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Total Synthesis Guided Structure Elucidation of (+)‐Psychotetramine

Cited by 121 publications

References 43 publications

Absolute configuration study of a new dimeric indole alkaloid from the leaves and twigs of Psychotria henryi

Absolute configuration study of a new dimeric indole alkaloid from the leaves and twigs of Psychotria henryi

A Mild and General Larock Indolization Protocol for the Preparation of Unnatural Tryptophans

Nickel‐Catalyzed Barton Decarboxylation and Giese Reactions: A Practical Take on Classic Transforms

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