“…Compound 15 proved to be an excellent common intermediate for the generation of derivatives through facile nucleophilic ring opening by halides (16a–18a, see ESI † ) and cyanide (19a, see ESI † ), followed by hydrolysis of the N -sulfate ( Scheme 2B ). 40 The α-azide in these products was then reduced and Boc-protected to yield 16b–19b in moderate yields, likely due to steric congestion. To access additional derivatives, Boc-protected diamino lactone 12 was employed as a precursor instead.…”
The N-sulfonated monobactams harbor considerable potential to combat emerging bacterial infections that are problematic to treat due to their metallo-β-lactamase mediated resistance against conventional β-lactam antibiotics. Herein, we report a...
“…Compound 15 proved to be an excellent common intermediate for the generation of derivatives through facile nucleophilic ring opening by halides (16a–18a, see ESI † ) and cyanide (19a, see ESI † ), followed by hydrolysis of the N -sulfate ( Scheme 2B ). 40 The α-azide in these products was then reduced and Boc-protected to yield 16b–19b in moderate yields, likely due to steric congestion. To access additional derivatives, Boc-protected diamino lactone 12 was employed as a precursor instead.…”
The N-sulfonated monobactams harbor considerable potential to combat emerging bacterial infections that are problematic to treat due to their metallo-β-lactamase mediated resistance against conventional β-lactam antibiotics. Herein, we report a...
“…As part of the initial development work, it was hoped that forming an alternative organometallic might be more tolerant of warmer temperatures. However, alternative organometallic reagents (Grignard and cuprates) proved to be poorly reactive with cyclic sulfamidate 3 , and the approach was abandoned . Focus was returned to organolithium–cyclic sulfamidate chemistry, aiming to improve the yield and remove the isolation of protected amine 4 .…”
Camizestrant is currently being investigated in multiple Phase 3 clinical trials for ER+ breast cancer. This article describes our efforts toward the first manufacture of clinical material. Strategic process development focused on delivering robust processes and control points that could be scaled to deliver kilograms of material of the right quality and meet expedited project timelines. Highlights include optimization of an efficient Buchwald−Hartwig amination, development of a diastereoselective Pictet− Spengler reaction followed by an efficient isolation, and a significant reduction in the number of chromatography stages from five to one. The processes were used to deliver 8.5 kg of material in an overall yield of 44%.
“…The application of ring-opening strategies has also been demonstrated in the synthesis of β-fluoroalanines and difluoroglutamic acid derivatives by Bolek and Ignatowska ( Scheme 31 ) [ 117 ]. Starting with the cylic sulfamidate 143 , ring-opening was achieved using a mixture of copper, BrCF 2 CO 2 Et and TMEDA.…”
“…Using the same approach with N -morpholine bromodifluoroacetamide, the novel amino acid 147 was obtained in 14 % yield. Scheme 31 Access to β-fluoroalanines and difluoroglutamic acid derivatives, Bolek and Ignatowska [ 117 ]. …”
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