Synthesis of Chiral Dihydrobenzofurans and Phthalides by Asymmetric Transfer Hydrogenation via Dynamic Kinetic Resolution: A Strategy for Total Synthesis of Daldinins A, B, and C and Concentricolide

Abstract

Av ersatile and efficients trategyf or the total synthesis of the anti-HIV-1 agent concentricolide and its analogues daldinins A, B, and Ch as been established.T his strategy offersamild and facile access to these benzo annulated compounds, bearing multiple stereocenters in good yield with 99% enantiomeric excess (ee)a nd 93% diastereomeric excess( de)v alues. Construction of the corresponding syn dihydrobenzofuran andp hthalide groups can be achieved in one step by Noyoris asymmetric transfer hydrogenation, via dynamic kinetic resolution.

Escaping from Flatland: Stereoconvergent Synthesis of Three‐Dimensional Scaffolds via Ruthenium(II)‐Catalyzed Noyori–Ikariya Transfer Hydrogenation

“…[45] In their endeavors to access (À)-daldinin A, Fang et al developed af inal step DKR-ATHt oe stablish three transanular stereocenters in one chemical operation ( Figure 26). [46] The latestage chiral induction was crucial because the chiral g-lactone motif was prone to racemization in alkaline reactionc onditions of the Dieckmann condensation used to construct the benzofuran moiety.D uring the DKR-ATH of 109,t wo modes of epimerization were driving the Curtin-Hammett equilibrium: keto-enol tautomerism and an elimination-additione quilibrium of the lactone. [47] Am ixture of daldinin A( 110)( 91 %, 93 % ee) and am inor diastereomer (9 %, 83 % ee)w as thus obtained in 78 %i solated yield.…”

Recent Progress and Applications of Transition-Metal-Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation of Ketones and Imines through Dynamic Kinetic Resolution

“…In 2016, Fang and co-workers achieved a practical access to a series of cis-benzoannulated compounds using ATH, via DKR. 35 This novel, mild and general synthetic route allowed access to a novel structural class of significance in medicinal chemistry, including daldinins A, B, and C natural products (10.1%, 7.6%, 6.8% overall yields, respectively). R. Molina Betancourt et al…”

Total Synthesis, Discovery and Biological Evaluation of Daldinin A Derivatives for Improving Hyperglycemia-Induced Endothelial Cell Death

“…2) Annulatins isolated from the culture medium of Cordyceps annullata in the presence of a histone deacetylase (HDAC) inhibitor exhibited potent agonistic activity toward cannabinoid receptors. 3,4) The families of naturally-occurring tricyclic heterocycles have been reported to exert a wide range of activities. Despite this, the bioactivity of daldinins has yet to be fully elucidated, indicating the magnitude of our lack of knowledge regarding these tricyclic heterocycles.…”