Details

Autor(en) / Beteiligte

• Allentoff, Alban J.
• Wallace, Michael A.
• Traeger, Sarah C.
• Zheng, Naiyu
• Zhang, Qian
• Bonacorsi, Samuel J.

Titel

Synthesis of an adenine N-3 substituted CBI adduct by alkylation of adenine with a 1-iodomethylindoline seco-CBI precursor

Ist Teil von

• Tetrahedron, 2018-11, Vol.74 (46), p.6680-6688

Ort / Verlag

Elsevier Ltd

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The synthesis of a 1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI)-adenine adduct via regioselective N-3 alkylation of adenine with a 1-(iodomethyl)-2,3-dihydro-1H-benzo[e]indol-5-ol (I-seco-CBI)-containing precursor is described. Spectroscopic analyses of the unlabeled and adenine-C8 carbon-13 labeled adducts utilizing ROESY NMR techniques allowed structural assignment of the alkylation product as the adenine N-3 substituted regioisomer. A stable-isotopically labeled version of the N-3 adduct incorporating six carbon-13 labels was also prepared by this method for use as an LC-MS internal standard. The cyclized CBI-containing compound was also found to alkylate adenine at elevated temperatures to produce the N-3 adduct albeit at a significantly slower rate than that observed for the I-seco-CBI precursor. Adenine alkylation with an I-seco-CBI precursor offers scalable and facile access to a CBI-adenine adduct facilitating its use as an efficacy marker for the development of duocarmycin-based ADCs. [Display omitted]