84573-16-0 Usage
Description
Rocaglamide is an anti-inflammatory, insecticidal, and anticancer tetrahydrobenzofuran isolated from Aglaia species. It has been shown to inhibit both TNF-α and the activation of NF-κB in Jurkat T cells with IC50 values in the nanomolar range. At 25 nM, rocaglamide induces apoptosis in various human leukemia cell lines, activating p38 MAPK/JNK and suppressing ERK. Rocaglamide also reduces IFN-γ, TNF-α, IL-2, and IL-4 production in peripheral blood T cells at a concentration of 50 nM. Furthermore, rocaglamide can inhibit the T cell expression of the immune response transcription factor, nuclear factor of activated T cells.
Uses
Rocaglamide is derived from a Chinese medicinal plant Aglaia. Rocaglamide induces apoptosis in various human leukemia cell lines and in acute lymphoblastic leukemia, chronic myeloid leukemia and acute myeloid leukemia cells freshly isolated from patients.
Definition
ChEBI: An organic heterotricyclic compound that is 2,3,3a,8b-tetrahydro-1H-benzo[b]cyclopenta[d]furan substituted by hydroxy groups at positions 1 and 8b, methoxy groups at positions 6 and 8, a 4-methoxyphenyl group at
position 3a, a phenyl group at position 3 and a N,N-dimethylcarbamoyl group at position 1. Isolated from Aglaia odorata and Aglaia duperreana, it exhibits antineoplastic activity.
General Description
Rocaglamide is known to be derived from tetrahydro benzofuran and is also an active chemical compound of Aglaia plants.
Biochem/physiol Actions
Rocaglamide is a potent anticancer agent isolated from the genus Aglaia. Rocaglamides inhibit protein synthesis without affecting DNA or RNA synthesis. Recent study shows that Rocaglamide binds to prohibitin (PHB) 1 and 2, which prevents interaction between PHB and CRaf and inhibits CRaf activation and subsequently CRaf-MEK-ERK signaling. Also, Rocaglamide is an immunosuppressant that inhibits activation of NF-kB and NF-AT.
References
1) Baumann?et al.?(2002),?Rocaglamide Derivatives Are Potent Inhibitors of NF-kB Activation in T-cells; J. Biol. Chem.?277?44791
2) Prolsch?et al.?(2005),?Rocaglamide Derivatives Are Immunosuppressive Phytochemicals That Target NF-AT Activity in T Cells; J. Immunol.?174?7075
3) Polier?et al.?(2012),?The natural anticancer compounds rocaglamides inhibit the Raf-MEK-ERK pathway by targeting prohibitin1 and 2; Chem. Biol.?19?1093
4) Neumann?et al.?(2014),?The natural anticancer compound rocaglamide selectively inhibits the G1-S phase transition in cancer cells through the ATM/ATR-mediated Chk1/2 cell cycle checkpoints; Int. J. Cancer?134?1991
5) Zhu?et al.?(2007),?The traditional Chinese herbal compound rocaglamide preferentially induces apoptosis in leukemia cells by modulation of mitogen-activated protein kinase activities; Int. J. Cancer?121?1839
Check Digit Verification of cas no
The CAS Registry Mumber 84573-16-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,4,5,7 and 3 respectively; the second part has 2 digits, 1 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 84573-16:
(7*8)+(6*4)+(5*5)+(4*7)+(3*3)+(2*1)+(1*6)=150
150 % 10 = 0
So 84573-16-0 is a valid CAS Registry Number.
InChI:InChI=1/C29H31NO7/c1-30(2)27(32)23-24(17-9-7-6-8-10-17)29(18-11-13-19(34-3)14-12-18)28(33,26(23)31)25-21(36-5)15-20(35-4)16-22(25)37-29/h6-16,23-24,26,31,33H,1-5H3/t23-,24?,26-,28+,29+/m1/s1
84573-16-0Relevant articles and documents
The Evolution of the Total Synthesis of Rocaglamide
Zhou, Zhe,Dixon, Darryl D.,Jolit, Anais,Tius, Marcus A.
, p. 15929 - 15936 (2016/10/24)
The complex flavagline, (?)-rocaglamide, possesses a synthetically intriguing tricyclic scaffold with five contiguous stereocenters and also exhibits potent anticancer, anti-inflammatory and insecticidal activity. This full account details distinct approaches to (±)- and (?)-rocaglamide utilizing Br?nsted acid catalyzed and asymmetric Pd0-catalyzed Nazarov chemistry developed in our laboratory, respectively. The successful asymmetric synthesis revealed unforeseen mechanistic complexity that required adjusting our strategy to overcome an unanticipated racemization process, an unusual reversible ring-cleavage step and a very facile trialkylsilyl group migration.
Total synthesis of (±)-rocaglamide via oxidation-initiated nazarov cyclization
Malona, John A.,Cariou, Kevin,Spencer, William T.,Frontier, Alison J.
experimental part, p. 1891 - 1908 (2012/04/23)
This article describes the evolution of a Nazarov cyclization-based synthetic strategy targeting the anticancer, antiinflammatory, and insecticidal natural product (±)-rocaglamide. Initial pursuit of a polarized heteroaromatic Nazarov cyclization to construct the congested cyclopentane core revealed an unanticipated electronic bias in the pentadienyl cation. This reactivity was harnessed in a successful second-generation approach using an oxidation-initiated Nazarov cyclization of a heteroaryl alkoxyallene. Full details of these two approaches are given, as well as the characterization of undesired reaction pathways available to the Nazarov cyclization product. A sequence of experiments that led to an understanding of the unexpected reactivity of this key intermediate is described, which culminated in the successful total synthesis of (+)-rocaglamide.
Total synthesis and biological activity of (±)-rocaglamide and its 2,3-di-epi analogue
Li, Hongsen,Fu,Wang,Li,Liu,Xie,Ma,Qin, Zhaohai
experimental part, p. 1753 - 1758 (2009/04/07)
By introducing the strategy of intramolecular reductive coupling to construct the cyclopenta[b]benzofuran skeleton, the shortest and most efficient synthetic method hitherto was now established to rocaglamide 1 and its 2,3-di-epi analogue 3 in racemic form by Michael addition, SmI 2-promoted intramolecular keto-ester coupling, amination of the ester intermediate, and reduction of carbonyl with Me4NBH(OAc) 3. Several steps were highly stereoselective or even stereospecific. The bioassay results indicated that both 1 and 3 were much better repellents against Plutella xylostella than azadirachtin; the insecticidal activity of 1 was higher than that of azadirachtin against Pieris rapae, P. xylostella, Laphygma exigua, and Helicoverpa armigera, but that of 3 was lower. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
