The first total synthesis of lymphostin

Tatsuta, Kuniaki; Imamura, Kiyoshi; Itoh, Sayaka; Kasai, Soko

doi:10.1016/j.tetlet.2004.01.140

Cited by 25 publications

(17 citation statements)

References 9 publications

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“…The pyrroloiminoquinone core itself is proposed to originate from tryptophan [24], which is also the initial precursor in the biosynthetic pathway leading to the related pyrroloquinoline, lymphostin, produced by the marine bacterium Salinispora sp. [25]. This, together with the conservation of dominant bacterial symbionts in the microbiomes of multiple pyrroloiminoquinone-producing Tsitsikamma species [26], has led to the suggestion that the biogenetic origin of pyrroloiminoquinones in latrunculid sponges may be microbial.…”

Section: Introductionmentioning

confidence: 99%

Molecular Networking Reveals Two Distinct Chemotypes in Pyrroloiminoquinone-Producing Tsitsikamma favus Sponges

et al. 2019

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The temperate marine sponge, Tsitsikamma favus, produces pyrroloiminoquinone alkaloids with potential as anticancer drug leads. We profiled the secondary metabolite reservoir of T. favus sponges using HR-ESI-LC-MS/MS-based molecular networking analysis followed by preparative purification efforts to map the diversity of new and known pyrroloiminoquinones and related compounds in extracts of seven specimens. Molecular taxonomic identification confirmed all sponges as T. favus and five specimens (chemotype I) were found to produce mainly discorhabdins and tsitsikammamines. Remarkably, however, two specimens (chemotype II) exhibited distinct morphological and chemical characteristics: the absence of discorhabdins, only trace levels of tsitsikammamines and, instead, an abundance of unbranched and halogenated makaluvamines. Targeted chromatographic isolation provided the new makaluvamine Q, the known makaluvamines A and I, tsitsikammamine B, 14-bromo-7,8-dehydro-3-dihydro-discorhabdin C, and the related pyrrolo-ortho-quinones makaluvamine O and makaluvone. Purified compounds displayed different activity profiles in assays for topoisomerase I inhibition, DNA intercalation and antimetabolic activity against human cell lines. This is the first report of makaluvamines from a Tsitsikamma sponge species, and the first description of distinct chemotypes within a species of the Latrunculiidae family. This study sheds new light on the putative pyrroloiminoquinone biosynthetic pathway of latrunculid sponges.

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Section: Introductionmentioning

confidence: 99%

Molecular Networking Reveals Two Distinct Chemotypes in Pyrroloiminoquinone-Producing Tsitsikamma favus Sponges

et al. 2019

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“…This type of motif could also be found in natural products such as Murrayaquinone A ( E )– and BE 10988 ( F ) . Since the indolequinone moiety in molecule is believed to be related to the antitumor reactivity, several drugs such as Lymphostin ( G ), Discorhabdin C ( H ) and E09 ( I ), which can be regarded as derived from this notion, were explored (Figure ). Indeed, all these compounds exhibit stronger cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Palladium-Catalyzed C-H Functionalization of Amido-Substitued 1,4-Napthoquinone in the Presence of Amines toward the Formation of Pyrroles and Imidazoles

Chen

Hong

2017

ChemistrySelect

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Transition metal‐catalyzed ortho‐ C−H functionalization of amido‐substituted 1,4‐naphthoquinone, 3, in the presence of Pd(OAc)2 and tertiary amines led to the formations of 4 with newly generated pyrrole rings. Similar reactions were carried out with primary amines and yielded 5, having imidazole rings, as well as amination products 6. In the cases of reacting with secondary amines, the route for the formations of 4‐like, rather than 5‐type, products were prevailed. As revealed from the crystal structures of 4_Bu, 6_Bu, 6_Cy, and 4_Cy, cyclization processes indeed took place to form pyrrole and imidazole rings, respectively, which are fused to the former naphthoquinone framework. The crystal structure of 5_Cy shows that it is a product from amination reaction. Similar reaction was carried out using PCy3 as the phosphine source and an unexpected product 7 was obtained. The crystal structure of 7 exhibits that the moiety of PCy3 attaches to the framework of the former naphthoquinone and brings about a new P=C double bond. In addition, the amide fragment of 3 is hydrolyzed and reduced and forms C=N double bond. Here, distinct reactivity of amines from that of phosphines in this type of reactions have been manifested.

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“…108 The first total synthesis of 201 has been achieved from the tryptophan derivative 202 by means of six regioselective oxidation reactions (Scheme 37). 109 The critical step is the construction of the tricyclic core 204 from the quinone 203 by cyclization and oxidation.…”

Section: Physostigmine and Related Compoundsmentioning

confidence: 99%