660396-67-8Relevant academic research and scientific papers
Synthesis of lamellarin alkaloids using orthoester-masked α-keto acids
Shirley, Harry J.,Koyioni, Maria,Muncan, Filip,Donohoe, Timothy J.
, p. 4334 - 4338 (2019/04/17)
Pyruvic acid and other α-keto acids are frequently encountered as intermediates in metabolic pathways, yet their application in total synthesis has met with limited success. In this work, we present a bioinspired strategy that utilizes highly functionaliz
Total Synthesis of Lamellarin D Trimethyl Ether, Lamellarin D, and Lamellarin H
Lade, Dhanaji M.,Pawar, Amit B.,Mainkar, Prathama S.,Chandrasekhar, Srivari
, p. 4998 - 5004 (2017/05/12)
Total syntheses of three different lamellarins have been accomplished using a Ru(II)-catalyzed (3 + 2) annulation strategy to construct the central pyrrole ring. The striking features of this synthesis are the use of PEG-400 as a green solvent for the (3
Concise Synthesis of Lamellarin Alkaloids by C-H/N-H Activation: Evaluation of Metal Catalysts in Oxidative Alkyne Annulation
Mei, Ruhuai,Zhang, Shou-Kun,Ackermann, Lutz
, p. 1715 - 1718 (2017/11/27)
The performance of various transition-metal catalysts was explored in the step-economical synthesis of naturally occurring lamellarin alkaloids by C-H/N-H activation. The oxidative alkyne annulation proceeded efficiently by using sustainable ruthenium(II) catalysis, which set the stage for a concise synthesis of lamellarin D, lamellarin H and derivatives thereof.
Synthesis of lamellarins via regioselective assembly of 1,2-diarylated [1]benzopyrano[3,4-b]pyrrol-4(3H)-one core
Fukuda, Tsutomu,Katae, Takatoshi,Harada, Issei,Iwao, Masatomo
, p. 950 - 971 (2017/07/28)
A modular synthesis of lamellarins has been developed. The key reactions in this synthesis are the assembly of 1,2-diarylated [1]benzopyrano- [3,4-b]pyrrol-4(3H)-ones from a preexisting [1]benzopyrano[3,4-b]pyrrol- 4(3H)-one core and the appropriate arylb
Total synthesis of lamellarins D, H, and R and ningalin B
Li, Qingjiang,Jiang, Jingqian,Fan, Aili,Cui, Yuxin,Jia, Yanxing
, p. 312 - 315 (2011/03/23)
A concise total synthesis of lamellarins D (7 steps), H (7 steps), and R (5 steps) and ningalin B (5 steps) is achieved starting from the corresponding aldehydes and amines. The synthesis features three oxidative reactions as key steps in a biomimetic manner, involving an AgOAc-mediated oxidative coupling reaction to construct the pyrrole core, a Pb(OAc)4-induced oxidative cyclization to form the lactone, and Kita's oxidation reaction to form the pyrrole-arene C-C bond.
Design and synthesis of lamellarin D analogues targeting topoisomerase I
Ohta, Takeshi,Fukuda, Tsutomu,Ishibashi, Fumito,Iwao, Masatomo
experimental part, p. 8143 - 8153 (2010/02/17)
(Chemical Equation Presented) A general synthetic route to rationally designed lamellarinDanalogues, 1-dearyllamellarinD(1) and 1-substituted 1-dearyllamellarin D (2), has been developed. The key pentacyclic intermediate 22 was prepared by palladium-catalyzed direct arylation of 12, which in turn was synthesized via C-2-selective lithiation of 15 followed by palladium-catalyzed cross-coupling as the key reactions. Compound 22 was converted to a wide range of C-1-substituted analogues 2 via regioselective electrophilic substitution and palladium-catalyzed cross-coupling reactions.
Total synthesis of lamellarins D, L, and N
Fujikawa, Naotaka,Ohta, Takeshi,Yamaguchi, Tomohiro,Fukuda, Tsutomu,Ishibashi, Fumito,Iwao, Masatomo
, p. 594 - 604 (2007/10/03)
Total synthesis of cytotoxic marine alkaloids, lamellarins D, L, and N, has been achieved by using Hinsberg-type pyrrole synthesis and palladium-catalyzed Suzuki-Miyaura coupling of the 3,4-dihydroxypyrrole bistriflate 6 as the key reactions. The total yields of lamellarins D, L, and N from the common intermediate 6 are 54, 58, and 50%, respectively.
Topoisomerase I-mediated DNA cleavage as a guide to the development of antitumor agents derived from the marine alkaloid lamellarin D: Triester derivatives incorporating amino acid residues
Tardy, Christelle,Facompre, Michael,Laine, William,Baldeyrou, Brigitte,Garcia-Gravalos, Dolores,Francesch, Andres,Mateo, Cristina,Pastor, Alfredo,Jimenez, Jose A.,Manzanares, Ignacio,Cuevas, Carmen,Bailly, Christian
, p. 1697 - 1712 (2007/10/03)
The marine alkaloid lamellarin D (LAM-D) has been recently characterized as a potent poison of human topoisomerase I endowed with remarkable cytotoxic activities against tumor cells. We report here the first structure-activity relationship study in the LAM-D series. Two groups of triester compounds incorporating various substituents on the three phenolic OH at positions 8, 14 and 20 of 6H-[1]benzopyrano[4′,3′:4,5]pyrrolo[2,1-a]isoquinolin-6- one pentacyclic planar chromophore typical of the parent alkaloid were tested as topoisomerase I inhibitors. The non-amino compounds in group A showed no activity against topoisomerase I and were essentially non cytotoxic. In sharp contrast, compounds in group B incorporating amino acid residues strongly promoted DNA cleavage by human topoisomerase I. LAM-D derivatives tri-substituted with leucine, valine, proline, phenylalanine or alanine residues, or a related amino side chain, stabilize topoisomerase I-DNA complexes. The DNA cleavage sites detected at T↓G or C↓G dinucleotides with these molecules were identical to that of LAM-D but slightly different from those seen with camptothecin which stimulates topoisomerase I-mediated cleavage at T↓G only. In the DNA relaxation and cleavage assays, the corresponding Boc-protected compounds and the analogues of the non-planar LAM-501 derivative lacking the 5-6 double bond in the quinoline B-ring showed no effect on topoisomerase I and were considerably less cytotoxic than the corresponding cationic compounds in the LAM-D series. The presence of positive charges on the molecules enhances DNA interaction but melting temperature studies indicate that DNA binding is not correlated with topoisomerase I inhibition or cytotoxicity. Cell growth inhibition by the 41 lamellarin derivatives was evaluated with a panel of tumor cells lines. With prostate (DU-145 and LN-CaP), ovarian (IGROV and IGROV-ET resistant to ecteinascidin-743) and colon (LoVo and LoVo-Dox cells resistant to doxorubicin) cancer cells (but not with HT29 colon carcinoma cells), the most cytotoxic compounds correspond to the most potent topoisomerase I poisons. The observed correlation between cytotoxicity and topoisomerase I inhibition strongly suggests that topoisomerase I-mediated DNA cleavage assays can be used as a guide to the development of superior analogues in this series. LAM-D is the lead compound of a new promising family of antitumor agents targeting topoisomerase I and the amino acid derivatives appear to be excellent candidates for a preclinical development.
ANTITUMORAL ANALOGS OF LAMELLARINS
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Page 103, (2010/02/06)
New lamellarins are provided of the general formula III wherein X is selected from the group consisting of N, O and S; wherein R1, R2, R3, R4, R5, R6, R7, R8 and Rsub
