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. 2015 Jan 8;56(2):458-460.
doi: 10.1016/j.tetlet.2014.11.126.

Facile syntheses of functionalized toll-like receptor 7 agonists

Babatope Akinbobuyi  1 , Matthew R Byrd  1 , Charles A Chang  2 , Mysa Nguyen  1 , Zacharie J Seifert  1 , Anne-Laure Flamar  3 , Gerard Zurawski  4 , Katherine C Upchurch  2 , SangKon Oh  4 , Stephen H Dempsey  5 , Thomas J Enke  5 , John Le  5 , Hunter J Winstead  5 , José R Boquín  5 , Robert R Kane  6
Affiliations

Facile syntheses of functionalized toll-like receptor 7 agonists

Babatope Akinbobuyi et al. Tetrahedron Lett. .

Abstract

Protein conjugates of toll-like receptor 7 agonists have been shown to elicit powerful immune responses. In order to facilitate our studies in this area our group has developed efficient syntheses for a number of functionalized derivatives that retain immune stimulatory activity.

Keywords: Adenine derivatives; Immune activation; Toll-like receptor; Vaccines.

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Figures

Figure 1
Figure 1
Synthetic TLR-7 agonists
Scheme 1
Scheme 1
Reagents and conditions: i. ArCH2Br, K2CO3, DMSO, rt, ii. n-BuONa/n-BuOH, reflux, iii. n-BuONa/n-BuOH, reflux, then add H2O, reflux, iv. Br2, CH2Cl2, rt 12 h or Br2, AcOH, AcONa, rt, 1 h.
Scheme 2
Scheme 2
Reagents and conditions: NaOH, CH3OH, reflux.
Scheme 3
Scheme 3
Reagents and conditions: i. CH3ONa, CH3OH, reflux, 61%, ii. HCl (conc), 43%, iii. HCl (conc), 15%.
Scheme 4
Scheme 4
Reagents and conditions: i. CH3ONa, CH3OH, reflux, 86%, ii. Pd(PPh3)2Cl2, CuI, Et3N, then propargyl alcohol, reflux, iii. NaI, TMSCl, CH3CN, reflux, iv. Pd(PPh3)2Cl2, CuI, Et3N, then BOC-propargyl amine, reflux, v. Pd/C, H2, MeOH, rt
Scheme 5
Scheme 5
Reagents and conditions: i. BOC-ethylenediamine, DIPEA, COMU, DMSO, DCM, 0°-rt, 2 h, ii. TFA, DCM, rt, 1 h, iii. BOC-NH-CH2CH2OCH2CH2OCH2CH2-NH2, DIPEA, COMU, DMSO, DCM, 0°-rt, 2 h.
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