Recent Advances in the Total Synthesis of Clavaminols

Abstract

Clavaminols are a new class of long-chain 2-amino-3-­alkanols that mostly contain 2R,3S-configurations. Owing to their interesting molecular architectures and promising activities, they have ­become popular targets for synthetic organic chemists. In this review, we highlight 12 total syntheses of clavaminols from different research groups during the period 2009 to 2018.1 Introduction2 Synthetic Approaches toward Clavaminols2.1 Total Synthesis by Chemla and Colleagues (2009)2.2 Total Synthesis by Greck and Colleagues (2010)2.3 Total Synthesis by Sutherland and Zaed (2011)2.4 Total Synthesis by Huang and Colleagues (2011)2.5 Total Synthesis by Kotora and Colleagues (2012)2.6 Total Synthesis by Kumar and Colleagues (2013)2.7 Total Synthesis by Prabhavathi Devi and Colleagues (2013 and 2016)2.8 Total Synthesis by Sarabia and Colleagues (2014)2.9 Total Synthesis by Mohapatra and Colleagues (2016)2.10 Total Synthesis by Lu and Colleagues (2016)2.11 Total Synthesis by Jin and Colleagues (2017)2.12 Total Synthesis by Kumar Pandey and Colleagues (2018)3 Conclusion

Total Synthesis of Natural Products and Medicinal Molecules via Chelation-Controlled Diastereoselective Hydride Reduction of Amino Ketones

“…Namely, reaction of L-tyrosine 26 with thionyl chloride in MeOH at reflux followed by protection of primary amine with BzCl resulted in ester, which underwent Weinreb amide formation process with Clavaminol A, a long-chain 2-amino-3-alkanols, was isolated from the Mediterranean ascidian Clavelina phlegraea, and showed significant cytotoxic bioactivities. 38 Very recently, our group completed 39,40 the efficient asymmetric syntheses of (-)-clavaminol A and deacetyl (+)-clavaminol H using chelation-controlled hydride reduction strategy including palladium catalyzed hydrogenation as the key steps. As illustrated in Scheme…”

Total Syntheses of Conhydrines via Ruthenium-Catalyzed Ring-Closing Metathesis (RCM) Reactions

“…Therefore, the synthesis of (−)--conhydrine was accomplished in 12 steps with 20% overall yield. HCl in the presence of AlMe3 followed by Grignard reaction with EtMgBr and chelation-controlled hydride reduction of resulting amino ketone using t Bu)3 as the reducing agent 55,56 in EtOH at -78 °C afforded anti-β-amino alcohol 80 as a single isomer in 84% yield for three steps. As shown in Figure 5, the stereochemistry of this reaction mechanism can be explained by the chelation of the aluminum ion to both the carbonyl oxygen and the amine nitrogen, enforcing a syn-periplanar relationship between the amine and ketone groups and lead to the anti--diastereomer.…”