Lomaiviticin A

• CAT Number: I030964
• CAS Number: 349662-86-8
• Molecular Formula: C68H82N6O24
• Molecular Weight: 1367.42
• Purity: 98%
• Synonyms: Lomaiviticin A
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Storage: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
• IUPAC Name: 11,11'-bis(diazo)-1,1'-bis((5-(dimethylamino)-4-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-1,2'-diethyl-6,6',9,9'-tetrahydroxy-2,2'-bis((5-hydroxy-4-methoxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-2,2',3,3'-tetrahydro-1H,1'H-[3,3'-bibenzo[b]fluorene]-4,4',5,5',10,10'(11H,11'H)-hexaone
• InChI: InChI=1S/C68H82N6O24/c1-13-67(97-37-20-32(80)56(74(9)10)24(4)92-37)51-46(45-48(54(51)72-70)62(86)42-30(78)18-16-28(76)40(42)60(45)84)63(87)50(66(67)96-36-21-33(89-11)57(81)25(5)93-36)52-64(88)44-43-47(61(85)41-29(77)17-15-27(75)39(41)59(43)83)53(71-69)49(44)65(95-35-19-31(79)55(73(7)8)23(3)91-35)68(52,14-2)98-38-22-34(90-12)58(82)26(6)94-38/h15-18,23-26,31-38,50,52,55-58,65-66,69-70,75-82H,13-14,19-22H2,1-12H3
• InChIKey: JVXAYSMFVOJEHL-UHFFFAOYSA-N
• SMILES: [NH-]=[N+]=c(c=12)c3c(C(C(C4C(c(c(=c5c(=O)c6c(O)ccc(O)c67)c7=O)c(C(OC8CC(O)C(N(C)C)C(C)O8)C4(OC9OC(C)C(O)C(OC)C9)CC)c5=[N+]=[NH-])=O)C(OC%10CC(OC)C(O)C(C)O%10)C3(CC)OC%11OC(C)C(N(C)C)C(O)C%11)=O)c1c(=O)c%12c(O)ccc(O)c%12c2=O

Lomaiviticin A is an antitumor antibiotic from Micromonospora lomaivitiensis; benzo(a)fluorene related to kinamycins.

Reference

1: Colis LC, Woo CM, Hegan DC, Li Z, Glazer PM, Herzon SB. The cytotoxicity of (-)-lomaiviticin A arises from induction of double-strand breaks in DNA. Nat Chem. 2014 Jun;6(6):504-10. doi: 10.1038/nchem.1944. Epub 2014 May 11. PubMed PMID: 24848236; PubMed Central PMCID: PMC4090708.
2: Waldman AJ, Balskus EP. Lomaiviticin biosynthesis employs a new strategy for starter unit generation. Org Lett. 2014 Jan 17;16(2):640-3. doi: 10.1021/ol403714g. Epub 2014 Jan 2. PubMed PMID: 24383813; PubMed Central PMCID: PMC3965344.
3: Feldman KS, Selfridge BR. Synthesis studies on the lomaiviticin A aglycone core: development of a divergent, two-directional strategy. J Org Chem. 2013 May 3;78(9):4499-511. doi: 10.1021/jo4005074. Epub 2013 Apr 15. PubMed PMID: 23581811.
4: Woo CM, Beizer NE, Janso JE, Herzon SB. Isolation of lomaiviticins C-E, transformation of lomaiviticin C to lomaiviticin A, complete structure elucidation of lomaiviticin A, and structure-activity analyses. J Am Chem Soc. 2012 Sep 19;134(37):15285-8. Epub 2012 Sep 10. PubMed PMID: 22963534.
5: Feldman KS, Selfridge BR. Enantioselective synthesis of the ent-lomaiviticin A bicyclic core. Org Lett. 2012 Nov 2;14(21):5484-7. doi: 10.1021/ol302567f. Epub 2012 Oct 17. PubMed PMID: 23075085.
6: Colis LC, Hegan DC, Kaneko M, Glazer PM, Herzon SB. Mechanism of action studies of lomaiviticin A and the monomeric lomaiviticin aglycon. Selective and potent activity toward DNA double-strand break repair-deficient cell lines. J Am Chem Soc. 2015 May 6;137(17):5741-7. doi: 10.1021/ja513117p. Epub 2015 Apr 22. PubMed PMID: 25849366; PubMed Central PMCID: PMC4845730.
7: Xue M, Herzon SB. Mechanism of Nucleophilic Activation of (-)-Lomaiviticin A. J Am Chem Soc. 2016 Dec 7;138(48):15559-15562. Epub 2016 Nov 28. PubMed PMID: 27934014; PubMed Central PMCID: PMC5339879.
8: Woo CM, Li Z, Paulson EK, Herzon SB. Structural basis for DNA cleavage by the potent antiproliferative agent (-)-lomaiviticin A. Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):2851-6. doi: 10.1073/pnas.1519846113. Epub 2016 Feb 29. PubMed PMID: 26929332; PubMed Central PMCID: PMC4801295.
9: Colis LC, Herzon SB. Synergistic potentiation of (-)-lomaiviticin A cytotoxicity by the ATR inhibitor VE-821. Bioorg Med Chem Lett. 2016 Jul 1;26(13):3122-3126. doi: 10.1016/j.bmcl.2016.04.090. Epub 2016 Apr 30. PubMed PMID: 27177826; PubMed Central PMCID: PMC4899226.
10: Morris WJ, Shair MD. Synthesis of the N-(tert-butyloxycarbonyl)-O-triisopropylsilyl-D-pyrrolosamine Glycal of Lomaiviticin A & B via Epimerization of L-Threonine. Tetrahedron Lett. 2010 Aug 18;51(33):4310-4312. PubMed PMID: 20802782; PubMed Central PMCID: PMC2926667.
11: Gholap SL, Woo CM, Ravikumar PC, Herzon SB. Synthesis of the fully glycosylated cyclohexenone core of lomaiviticin A. Org Lett. 2009 Oct 1;11(19):4322-5. doi: 10.1021/ol901710b. PubMed PMID: 19719089.
12: Wang B, Guo F, Ren J, Ai G, Aigle B, Fan K, Yang K. Identification of Alp1U and Lom6 as epoxy hydrolases and implications for kinamycin and lomaiviticin biosynthesis. Nat Commun. 2015 Jul 2;6:7674. doi: 10.1038/ncomms8674. PubMed PMID: 26134788; PubMed Central PMCID: PMC4506494.
13: Kersten RD, Lane AL, Nett M, Richter TK, Duggan BM, Dorrestein PC, Moore BS. Bioactivity-guided genome mining reveals the lomaiviticin biosynthetic gene cluster in Salinispora tropica. Chembiochem. 2013 May 27;14(8):955-62. doi: 10.1002/cbic.201300147. Epub 2013 May 3. PubMed PMID: 23649992; PubMed Central PMCID: PMC3755882.
14: Zhang W, Baranczak A, Sulikowski GA. Stereocontrolled assembly of the C3/C3′ dideoxy core of lomaiviticin A/B and congeners. Org Lett. 2008 May 15;10(10):1939-41. doi: 10.1021/ol800460a. Epub 2008 Apr 15. PubMed PMID: 18410121.
15: Laufer RS, Dmitrienko GI. Diazo group electrophilicity in kinamycins and lomaiviticin A: potential insights into the molecular mechanism of antibacterial and antitumor activity. J Am Chem Soc. 2002 Mar 6;124(9):1854-5. PubMed PMID: 11866589.
16: Woo CM, Gholap SL, Herzon SB. Insights into lomaiviticin biosynthesis. Isolation and structure elucidation of (-)-homoseongomycin. J Nat Prod. 2013 Jul 26;76(7):1238-41. doi: 10.1021/np400355h. Epub 2013 Jun 26. PubMed PMID: 23803003.
17: Nicolaou KC, Nold AL, Li H. Synthesis of the monomeric unit of the lomaiviticin aglycon. Angew Chem Int Ed Engl. 2009;48(32):5860-3. doi: 10.1002/anie.200902509. PubMed PMID: 19575434; PubMed Central PMCID: PMC2775545.
18: Krygowski ES, Murphy-Benenato K, Shair MD. Enantioselective synthesis of the central ring system of lomaiviticin A in the form of an unusually stable cyclic hydrate. Angew Chem Int Ed Engl. 2008;47(9):1680-4. doi: 10.1002/anie.200704830. PubMed PMID: 18214870.
19: Surovtseva YV, Jairam V, Salem AF, Sundaram RK, Bindra RS, Herzon SB. Characterization of Cardiac Glycoside Natural Products as Potent Inhibitors of DNA Double-Strand Break Repair by a Whole-Cell Double Immunofluorescence Assay. J Am Chem Soc. 2016 Mar 23;138(11):3844-55. doi: 10.1021/jacs.6b00162. Epub 2016 Mar 9. PubMed PMID: 26927829; PubMed Central PMCID: PMC5530877.
20: Lee HG, Ahn JY, Lee AS, Shair MD. Enantioselective synthesis of the lomaiviticin aglycon full carbon skeleton reveals remarkable remote substituent effects during the dimerization event. Chemistry. 2010 Nov 22;16(44):13058-62. doi: 10.1002/chem.201002157. PubMed PMID: 20976820; PubMed Central PMCID: PMC3152949.