Enantioselective Synthesis of the Ethyl Analog of the Marine Alkaloid Haliclorensin C

Guillaume Guignard; Núria Llor; David Pubill; Joan Bosch; Mercedes Amat

doi:10.3390/molecules24061069

Enantioselective Synthesis of the Ethyl Analog of the Marine Alkaloid Haliclorensin C

Molecules. 2019 Mar 18;24(6):1069. doi: 10.3390/molecules24061069.

Authors

Guillaume Guignard¹, Núria Llor², David Pubill³, Joan Bosch⁴, Mercedes Amat⁵

Affiliations

¹ Laboratory of Organic Chemistry, Department of Pharmacology, Toxicology, and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, and Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain. guignard.guillaume@gmail.com.
² Laboratory of Organic Chemistry, Department of Pharmacology, Toxicology, and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, and Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain. nllor@ub.edu.
³ Pharmacology Section, Department of Pharmacology, Toxicology, and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, and Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain. d.pubill@ub.edu.
⁴ Laboratory of Organic Chemistry, Department of Pharmacology, Toxicology, and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, and Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain. joanbosch@ub.edu.
⁵ Laboratory of Organic Chemistry, Department of Pharmacology, Toxicology, and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, and Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain. amat@ub.edu.

Abstract

The enantioselective synthesis (3.7% overall yield in nine steps from 2) and biological screening of the ethyl analog of the macrocyclic marine alkaloid haliclorensin C (compound 5) are reported. Amino alcohol 3, generated by a LiNH₂BH₃-promoted reductive ring-opening/debenzylation sequence from phenylglycinol-derived lactam 2, was used as the starting chiral linear building block. Incorporation of the undecene chain via the nosyl derivative 12, methylenation of the pentanol moiety, and a ring-closing metathesis are the key steps of the synthesis.

Keywords: alkaloids; amino alcohols; enantioselective synthesis; macrocycle; reduction; ring opening.

MeSH terms

Alkaloids / chemical synthesis*
Alkaloids / chemistry*
Aquatic Organisms / chemistry*
Ethyl Chloride / chemistry*
Stereoisomerism

Substances

Alkaloids
haliclorensin C
Ethyl Chloride