Samarium(II) dibromide-promoted selective deprotection of a benzoyl protective group

<p>The selective deprotection of a benzoyl group was very important methodology in the field of organic synthesis. Various methods for debenzoylation were investigated and developed in the past six decades, but more useful and selective strategies are now being strongly desired. In response to this strong demand, we developed the novel and selective deprotection of a benzoyl group by use of samarium(II) dibromide and a proton source. This deprotective reaction proceeded smoothly and the desired compound was obtained in good to excellent yields. In this paper, we will report the details of this deprotective reaction.</p

Chemical structures of aspartame (A), α-L-aspartyl-D-phenylalanine methyl ester (L, D-APM) (B), α-D-aspartyl-L-phenylalanine methyl ester (D, L-APM) (C), and α-D-aspartyl-D-phenylalanine methyl ester (D, D-APM) (D).

<p>Chemical structures of aspartame (A), α-L-aspartyl-D-phenylalanine methyl ester (L, D-APM) (B), α-D-aspartyl-L-phenylalanine methyl ester (D, L-APM) (C), and α-D-aspartyl-D-phenylalanine methyl ester (D, D-APM) (D).</p

The L, D-APM and/or D, L-APM contents of commercially available L, L-APM samples.

<p>The L, D-APM and/or D, L-APM contents of commercially available L, L-APM samples.</p

Representative HPLC chromatograms of an L, L-APM standard solution spiked with L, D-APM of 0.04 wt% (A, B, and C), L, D-APM (D), D, L-APM (E), L, L-APM (F), and D, D-APM (G) (all standard solutions; 0.2 μg/mL).

<p>Chromatograms A, D, E, F, and G were obtained using the L-column2 ODS column (column 1). Chromatograms B and C were obtained using the TSK-gel ODS 80 Ts column (column 2) and Mightysil RP-18 GP column (column 3), respectively. The peaks labeled 1 and 2 in chromatograms A—C correspond to L, D-APM and L, L-APM, respectively.</p

Detection of Y93H RAV by direct sequencing at baseline and during SMV/PR therapy.

<p>BT, breakthrough;</p><p>SVR, sustained virological response</p><p>*within 7 days of the initiation of treatment, when HCV RNA was still detectable,</p><p>**at least 3 months after the end of treatment</p><p>Detection of Y93H RAV by direct sequencing at baseline and during SMV/PR therapy.</p

Changes in the proportion of Y93H RAV within each individual.

<p>The proportion of Y93H RAV over the Y93 wild type within each patient was determined by deep sequencing at baseline and at an early time point during SMV/PR therapy (within 7 days). The mean proportion of Y93H RAV was 52.7% at baseline and 29.7% during therapy (p = 0.023). The proportion of Y93H was reduced in 21 of 29 cases (72.4%, solid lines). In contrast, Y93H percentages increased in 8 cases (27.6%, broken lines).</p

HCV RNA reduction of Y93H RAV versus the Y93 wild type during SMV/PR therapy.

<p>Reduction of HCV RNA from baseline to an early time point during SMV/PR therapy was determined for Y93H RAV and the Y93 wild type. Within 7 days of the initiation of therapy, HCV RNA reduction was significantly greater for Y93H RAV (-3.7 ± 1.3 logIU/mL/day) than the Y93 wild type (-3.4 ± 1.0 logIU/mL/day) (p<0.001).</p

Factors associated with rapid fibrosis progression.

<p>Factors associated with rapid fibrosis progression.</p

Changes in the proportion of Y93H RAV in 4cases with breakthrough or relapse.

<p>Deep sequencing was performed in 4 patients with relapse (a) or breakthrough (b, c, d) to quantify the proportion of Y93H RAV against the Y93 wild type. In two cases, PR therapy was continued up to 24 wks after stopping SMV (b and c). The proportion of Y93H RAV decreased during SMV/PR therapy and at the time of breakthrough/relapse compared to baseline but recovered to the baseline level at follow up. PR therapy; pegylated interferon plus ribavirin therapy, SMV/PR therapy; Simeprevir plus pegylated interferon / ribavirin therapy</p

Association of SNPs genotype with fibrosis progression rate.

<p>Error bars indicate the standard error.</p