Discorhabdins and Pyrroloiminoquinone-Related Alkaloids

Hu, Jin‐Feng; Fan, Hui; Xiong, Juan; Wu, Shi‐Biao

doi:10.1021/cr100435g

Cited by 135 publications

(107 citation statements)

References 156 publications

(819 reference statements)

Supporting

Mentioning

102

Contrasting

Order By: Relevance

“…Examples include the well known natural product mitomycin C (MMC) used clinically for the treatment of solid tumours, 1 the synthetic MMC analogue EO9 (apaziquone, EOquin) currently being trialled as a treatment for bladder cancer, 2, 3 and the antitumour zyzzyanone B and related pyrroloindolequinone natural products (Figure 1). 4 Hence indolequinones have attracted considerable interest in the anticancer arena not only as cytotoxins, but also as bioreductively activated prodrugs. 5–8 In continuation of our studies on the synthesis and biology of indolequinones, we investigated a number of relatively simple tri- and tetra-substituted derivatives initially evaluating their cytotoxicity and also their metabolism by quinone reductase enzymes.…”

Section: Introductionmentioning

confidence: 99%

Antitumour indolequinones: synthesis and activity against human pancreatic cancer cells

et al. 2014

View full text Add to dashboard Cite

An important determinant of the growth inhibitory activity of indolequinones against pancreatic cancer cells is substitution on the 2-position with 2-unsubstituted derivatives being markedly more potent. A series of indolequinones bearing a range of substituents on nitrogen and at the indolylcarbinyl position was prepared by copper(II)-mediated reaction of bromoquinones and enamines, followed by functional group interconversions. The compounds were then assayed for their ability to inhibit the growth of pancreatic cancer cells. The pKa of the leaving group at the 3-position was shown to influence growth inhibitory activity that is consistent with the proposed mechanism of action of reduction, loss of leaving group and formation of a reactive iminium species. Substitutions on the indole nitrogen were well tolerated with little influence on growth inhibitory activity while substitutions at the 5- and 6- positions larger than methoxy led to decreased activity. The studies presented define the range of substitutions of 2-unsubstituted indolequinones required for optimal growth inhibitory activity.

show abstract

Section: Introductionmentioning

confidence: 99%

Antitumour indolequinones: synthesis and activity against human pancreatic cancer cells

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The characteristic chemical shift of C9 ( δ 147.3) indicated an amino substitution on the α-position of the carbonyl group, which was commonly found in pyrroloiminoquinone derivatives. 4–8 This assignment was verified by an HMBC correlation from H ( δ 5.23) to C9; the carbon ( δ 90.2) was thus arranged as C14 connecting to the pyrroloiminoquinone core through N13. This arrangement was also supported by the HMBC correlation from H14 to C24.…”

mentioning

confidence: 75%

“…3 Other bioactivities of this alkaloid class include antimicrobial, antiviral, antimalarial, caspase inhibition, feeding deterrence, and immunomodulatory. 4 These utilities together with the highly strained ring system have attracted a broad range of interests. Several total syntheses of this alkaloid class have been developed, including discorhabdin A, 5 makaluvamine D, 6 and other derivatives.…”

mentioning

confidence: 99%

“…Acquiring from NMR experiments, the structure of the pyrroloiminoquinone motif was retained; 8 the rest of this molecule was changed dramatically from other reported pyrroloiminoquinone alkaloids. 1,4 …”

mentioning

confidence: 99%

“…Atkamine appears to utilize the common starting material and intermediate from the makaluvamine pathway. 4 It may derive from makaluvamine M, and the aliphatic side chain has possibly originated from ( Z )-15-docosenoic acid, a primary metabolite which was commonly found in sponge species with abundance. 15 Several key steps included an acylation between the enamine moiety and the FA source, 16 the formation of a quinone methide intermediate, 17 consecutive conjugate additions, 18 and a finally reductive cyclization.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Atkamine: A New Pyrroloiminoquinone Scaffold from the Cold Water Aleutian Islands Latrunculia Sponge

Zou

Hamann

2013

Org. Lett.

View full text Add to dashboard Cite

A new pyrroloiminoquinone alkaloid, named atkamine, with an unusual scaffold was discovered from a cold, deep water Alaskan sponge Latrunculia sp. collected from the Aleutian Islands. Olefin metathesis was utilized to determine the location of the double bond in the hydrocarbon chain. The absolute configuration was determined by using computational approaches combing with the ECD (electronic circular dichroism) spectroscopy.

show abstract

Silver‐Catalyzed Carbon‐Phosphorus Functionalization for Polyheterocycle Formation

et al. 2017

View full text Add to dashboard Cite

Polyheterocycle construction with high diastereoselectivity by utilizing ar adical process is still problematic. In this communication,asilvercatalyzed carbon-phosphorus functionalization for polyheterocycle formation is described that furnishes good diastereoselectivity.V arious substituted 1-(1H-indol-1-yl)-3-phenylprop-2-en-1-ones and phosphineo xides were suitable for this transformation. This work avoids the installationo fd irect functional groups and thus makes full use of shorter and more efficient synthetic processes. Preliminary mechanistic investigations indicate that phosphorus radicals are involved by attacking the a-position of a,b-unsaturated carbonyl compounds to generate the desired products.Polyheterocycles are ubiquitous structural motifs found in natural productsa nd pharmaceuticals and also serve as valuable synthetic intermediates in the preparation of functional materials. [1,2] Owing to the extended heteroaromatic conjugated systems,p olyheterocycles and their derivatives are attracting tremendous attention directed to the developmento fs imple and efficient methodologies for theirc onstruction. [3,4] In the past, substantial advances were directedtoward efficient methods for these compounds by transition metal-catalyzed cyclization/functionalization approaches. Also,i th as emerged as one of the most importants ynthetic methodsb ecause of its particulare fficiency. [5] However, these approachess ufferf rom elaborately designed substrates and low functional group compatibility of polyheterocycles,thereby limiting their wide applications in organic chemistry research and industry.T hus,t he development of simple synthetic methods in which the polyheterocycle unit is constructed simultaneously via ar adical cyclization featuring facile operation and easily accessible starting materials remains relatively exploited but still challenging.Carbon-phosphorus functionalization has become one of the most important synthetic methodsf or the formation of phosphorus-containing compounds because many natural products or biomolecules contain these modified units in their structures.Atransition metal-catalyzed functionalization of the C-P bond by oxidative cross-coupling between C-H and P-H bonds willa void the installation of direct functional groups andt hus make full use of shorter and more efficient synthetic routes. [6][7][8][9] Despite considerable progress in the field, there still remain great challenges in oxidative C-H/P-H cross-coupling, [10][11][12][13] especially for obtainingg oodd iastereoselectivity in the polyheterocyclest hrough carbon-phosphorus functionalization. It is wellk nown that the phosphorus radical is electrophilic on generation from the oxidation of P-H bonds.W ee nvisioned that the phosphorus radical triggeredb yas ilver catalyst would easily attack the a-position of a,b-unsaturated carbonyl compounds owingt oi ts higher electrond ensity.T hereby an acarbon radical is formed by the intramolecular radical addition.L astly,t he active species is transformed into the polyheter...

show abstract

Discorhabdins and Pyrroloiminoquinone-Related Alkaloids

Cited by 135 publications

References 156 publications

Antitumour indolequinones: synthesis and activity against human pancreatic cancer cells

Antitumour indolequinones: synthesis and activity against human pancreatic cancer cells

Atkamine: A New Pyrroloiminoquinone Scaffold from the Cold Water Aleutian Islands Latrunculia Sponge

Silver‐Catalyzed Carbon‐Phosphorus Functionalization for Polyheterocycle Formation

Contact Info

Product

Resources

About