Investigation of Dearomatizing Spirocyclizations and Spirocycle Functionalization En Route to Spirocalcaridines A and B—Some Trials and Tribulations

Authors

• Ravi P. Singh, The University of Texas at Arlington
• Delphine Gout, The University of Texas at Arlington
• James X. Mao, The University of Texas at Arlington
• Peter Kroll, The University of Texas at Arlington
• Carl J. Lovely, Mississippi State University

ORCID

Singh: https://orcid.org/0000-0002-2900-5855; Mao: https://orcid.org/0009-0000-6043-5266; Kroll: https://orcid.org/0000-0003-4782-2805 Lovely: https://orcid.org/0000-0001-7012-2001

MSU Affiliation

College of Arts and Sciences; Department of Chemistry

Creation Date

2026-06-30

Abstract

Spirocalcaridines A and B are among the most challenging members of the marine invertebrate-derived Leucetta alkaloids. Approaches to the construction and elaboration of the highly compact spirocyclic core are described. The synthesis of tricyclic guanidine via tandem oxidative amination dearomatizing spirocyclization (TOADS) using hypervalent iodine set the stage for total synthesis via the migration of the C4/C8 double bond to the C4/C5 position, followed by oxidation. The undesired but not surprising propensity of the spirocyclic cyclohexadienone to undergo rearrangement to the phenol hindered the desired olefin migration. Furthermore, initial efforts to install the oxidation sequentially, first at C5 and then at C4 in the complete carbon skeleton, were fraught with unforeseen challenges and unusual outcomes. In addition, the scope and limitations of hypervalent iodine-mediated tandem oxidative dearomatizing spirocyclization on various substrates were explored. Urethanes and thiourethanes underwent spirocyclization with an excellent yield, whereas the reaction with allylic substrates and species lacking the p-methoxy substituent did not proceed. Attempts to prepare other guanidine precursors are briefly discussed.

Publication Date

3-2-2025

Publication Title

Molecules

Publisher

MDPI

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Rights

© 2025 The Authors

Recommended Citation

Singh, R.P.; Gout, D.; Mao, J.X.; Kroll, P.; Lovely, C.J. Investigation of Dearomatizing Spirocyclizations and Spirocycle Functionalization En Route to Spirocalcaridines A and B—Some Trials and Tribulations. Molecules 2025, 30, 1143. https://doi.org/10.3390/molecules30051143