A solid-state melt reaction (SSMR) has been demonstrated via a domino process for the synthesis of tetracyclic chromenopyran pyrimidinedione frameworks using Baylis-Hillman derivatives through in situ formation of an olefin followed by an intramolecular [4 + 2] cycloaddition reaction sequence. The tetracyclic frameworks were obtained without using catalyst and solvent in a highly stereoselective and stereospecific fashion. The isolated yield is excellent and does not require column chromatography purification to obtain the pure product.

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Calycosin, a bioactive isoflavonoid isolated from root extracts of Astragalus membranaceus, has been reported to inhibit melanogenesis, the mechanism of which remains undefined. In this study, we interrogated the mechanistic basis by which calycosin inhibits melanin production in two model systems, i.e., B16F10 melanoma cells and zebrafish embryos. Calycosin was effective in protecting B16F10 cells from α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis and tyrosinase activity. This anti-melanogenic effect was accompanied by decreased expression levels of microphthalmia-associated transcription factor (MITF), a key protein controlling melanin synthesis, and its target genes tyrosinase and tyrosinase-related protein-2 (TRP-2) in calycosin-treated cells. Mechanistically, we obtained the first evidence that calycosin-mediated MITF downregulation was attributable to its ability to block signaling pathways mediated by cAMP response element-binding protein (CREB) and p38 MAP kinase. The protein kinase A (PKA) inhibitor H-89 and p38 inhibitor SB203580 validated the premise that calycosin inhibits melanin synthesis and tyrosinase activity by regulating the PKA/CREB and p38 MAPK signaling pathways. Moreover, the in vivo anti-melanogenic efficacy of calycosin was manifested by its ability to suppress body pigmentation and tyrosinase activity in zebrafish embryos. Together, these data suggested the translational potential of calycosin to be developed as skin-lightening cosmeceuticals.

Key indicators: single-crystal X-ray study; T = 293 K; mean (C-C) = 0.003 Å; R factor = 0.045; wR factor = 0.133; data-to-parameter ratio = 14.6.In the title compound, C 28 H 22 O 6 , the chromeno ring system is almost planar, with a dihedral angle between the mean planes of the pyran and benzene rings of 1.87 (8) . The pyran ring bearing the methylphenyl substituent has a half-chair conformation while the other pyran ring has an envelope conformation with the tetrasubstituted C atom as the flap. The benzene ring of the chromeno ring system is inclined to the benzene ring fused to the latter pyran ring by 74.66 (9) . These aromatic rings are inclined to the 4-methylphenyl ring by 52.67 (9) and 66.63 (10) , respectively. In the crystal, molecules are linked via C-HÁ Á ÁO hydrogen bonds, forming a two-dimensional network parallel to the bc plane. Related literature

In the title compound, C24H21ClN2O6, the two fused six-membered pyran rings adopt half-chair conformations. The dihedral angle between the pyrimidine ring and the chloro­phenyl ring is 51.55 (3)°. In the crystal, mol­ecules are linked by pairs of weak inter­molecular C—H⋯O hydrogen bonds, forming inversion dimers. A C—H⋯π inter­action is also observed.