Cryptocaryols A–H, α-Pyrone-Containing 1,3-Polyols from Cryptocarya sp. Implicated in Stabilizing the Tumor Suppressor Pdcd4

Abstract

A high-throughput cell-based reporter assay designed to identify small-molecule stabilizers of the tumor suppressor Pdcd4 was used to screen extracts in the NCI Natural Products Repository. Bioassay-guided fractionation of an extract from a Papua New Guinea collection of the tropical tree Cryptocarya sp. provided a series of new 5,6-dihydro-α-pyrone-containing 1,3-polyols (1–8), named cryptocaryols A–H. Their structures were assigned from a combination of NMR, MS, and CD studies in conjunction with NMR database comparisons. Compounds 1–8 were found to rescue Pdcd4 from TPA-induced degradation with EC50 concentrations that ranged from 1.3 to 4.9 µM.

Cryptocaryols A and B: Total Syntheses, Stereochemical Revision, Structure Elucidation, and Structure–Activity Relationship

“…Next, we targeted the C-6 diastereomers of 1 and 2 ( 30a and 30b , respectively), as the stereochemical relationship between the C-6 and C-8 positions was ambiguously assigned by Gustafson. 7 Moreover, we found the greatest variance in the C-5 to C-9 positions in our comparison of the 1 H and 13 C NMR.…”

Total Synthesis of (+)-Cryptocaryol A Using a Prins Cyclization/Reductive Cleavage Sequence

“…2 Our group has previously reported the synthesis of some members of this family, including passifloricin, 3 (-)-pironetin, 4 strictifolione, 5 and fostriecin, 6 and more recently, we became interested in the synthesis of (+)-cryptocaryol A. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 7 These compounds have been reported to act as Pdcd4 (programmed cell death 4) stabilizers with EC 50 values between 1.3 and 4.9 µM, Pdcd4 being a tumorgenesis and invasion suppressor protein, 8,9,10,11 whose expression is down-regulated in several cancers. 12 Thus, the stabilization of the expression of Pdcd4 might help to improve the efficiency of chemotherapies.…”

Total Synthesis of Cryptorigidifoliol K: Confirmation of Structure and Absolute Configuration

“…The plant genus Cryptocarya (Lauraceae) includes over 200 species which are commonly distributed all over the tropical and subtropical regions of the world . Phytochemical studies on this species have led to the discovery of a variety of secondary metabolites, which include lignans, benzylisoquinolines,– proaporphine alkaloids,– flavonoids, cryptochinones, pavines,– and a variety of α ‐pyrone derivatives –.…”