Michellamine

Michellamine
IUPAC name (1R,3R,1’R,3’R)-5,5’-(1,1’-dihydroxy-8,8’-dimethoxy-6,6’-dimethyl-2,2’-binaphthalene-4,4’-diyl)bis(1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline-6,8-diol)
Identifiers
PubChem	454909
ChemSpider	400564
Jmol-3D images	Image 1
SMILES Oc1c8c(c(c(O)c1)c2cc(c(O)c3c2cc(cc3OC)C)c7c(O)c4c(cc(cc4OC)C)c(c5c(O)cc(O)c6c5C[C@H](N[C@@H]6C)C)c7)C[C@H](N[C@@H]8C)C
InChI InChI=InChI=1S/C46H48N2O8/c1-19-9-25-27(41-31-13-21(3) 47-23(5)39(31)33(49)17-35(41)51)15-29(45(53)43(25)37(11-19)55-7)30-16-28(26-10-20(2)12-38(56-8)44(26)46(30)54)42-32-14-22(4)48-24(6)40(32)34(50)18-36(42)52/h9-12,15-18,21-24,47-54H,13-14H2,1-8H3/t21-,22-,23-,24-/m1/s 1
Properties
Molecular formula	C46H48N2O8
Molar mass	756.882
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Michellamine is an atropisomeric alkaloid which has been found to be a strong anti-HIV viral replication inhibitor. It was discovered in the leaves of the Ancistrocladus korupensis which is a member of the Triphyophyllum peltatum found in Cameroon.^[1] There are 3 michellamines represented as A, B, and C, however, Michellamine B is the most active against the NID-DZ strain of HIV-2.^[2]

Occurrence

Michellamine A and B alkaloids occur naturally in Ancistrocladus korupensis leaves, a Triphyophyllum peltatum found in Cameroon. Bioactive chemical substances including alkaloids, tannins, and saponin are found in several plants in their roots, leaves, stems, flowers, or bark. Therapeutic chemicals have been found in various plants to treat diseases such as malaria, diabetes, and cancers.^[3]

Synthesis

There are 2 methods explored to synthesize Michellamines A and B. The first one, originally synthesized in 1994, is a retrosynthesis that leads to a biomimetic pathway that uses the construction of naphthalene/isoquinoline bonds before the naphthalene/naphthalene axis. The second method, originally synthesized only a few montes after the first method, is a complementary pathway that would use the naphthalene/naphthalene axis after it is created and add the 2 isoquinoline moieties.^[4]

Medical use

The main use of Michellamines are in anti-HIV medications. They inhibit viral replication of the Protein kinase C and virus-induced cellular fusion.^[5] They have a broad range of effectiveness across most HIV strains, particularly the HIV-2 strain, which is found primarily in and around Cameroon.^[5]

References

1. ^ Schlauer, Jan; et al. (1). "Characterization of Enzymes fromAncistrocladus (Ancistrocladaceae) and Triphyophyllum (Dioncophyllaceae) Catalyzing Oxidative Coupling of Naphthylisoquinoline Alkaloids to Michellamines,, ,". Archives of Biochemistry and Biophysics 350 (1): 87–94. doi:10.1006/abbi.1997.0494. 
2. ^ Zhang, Heping; Zembower, David. Chen, Zhidong (NaN undefined NaN). "Structural analogues of the michellamine anti-HIV agents. Importance of the tetrahydroisoquinoline rings for biological activity". Bioorganic & Medicinal Chemistry Letters 7 (20): 2687–2690. doi:10.1016/S0960-894X(97)10057-9. 
3. ^ Okigbo, R. N.; C. L. Anuagasi and J. E. Amadi (February 2009). "Advances in selected medicinal and aromatic plants". Journal of Medicinal Plants Research 3(2): 86–95. http://www.academicjournals.org/jmpr/PDF/pdf2009/Feb/Okigbo%20et%20al.pdf. Retrieved April 6, 2011. 
4. ^ Bringmann, Gerhard; Götz, Roland, Keller, Paul A., Walter, Rainer, Boyd, Michael R., Lang, Fengrui, Garcia, Alberto, Walsh, John J., Tellitu, Imanol, Bhaskar, K. Vijaya, Kelly, T. Ross (NaN undefined NaN). "A Convergent Total Synthesis of the Michellamines". The Journal of Organic Chemistry 63 (4): 1090–1097. doi:10.1021/jo971495m. 
5. ^ ^{a b} White, E.; Chao, W. R.; Ross, L. J.; Borhani, D. W.; Hobbs, P. D.; Upender, V.; Dawson, M. I. (1999). "Michellamine Alkaloids Inhibit Protein Kinase C". Archives of Biochemistry and Biophysics 365 (1): 25–30. doi:10.1006/abbi.1999.1145. PMID 10222035.  edit