Two methods for the synthesis of vaulted biaryls were developed involving the reactions of carbene complexes with alkynes and the [2 + 2] cycloaddition of ketenes. The final step in the synthesis of 3,3‘-diphenyl-[2,2‘-binaphthalene]-1,1‘-diol (39) and 2,2‘-diphenyl-[3,3‘-biphenanthrene]-4,4‘-diol (47) (VAPOL) was phenol coupling of the 3-phenyl-1-naphthol (14) and the 2-phenyl-4-phenanthrol (28), respectively. The naphthol 14 could be prepared from the thermolysis of phenylacetyl chloride in the presence of phenylacetylene or from the benzannulation of the pentacarbonyl(phenylmethoxymethylene)chromium(0) (15) with phenylacetylene which upon an acetylative workup gives O-acetyl-4-methoxy-2-phenyl-1-naphthol (16). The reductive cleavage of the acetoxy group in 16 was unexpectedly affected by aluminum chloride and ethanethiol which were used to cleave the methyl ether. In a similar manner, the phenanthrol 28 could either be prepared from the 1-naphthylacetyl chloride (30) or pentacarbonyl(1-naphthylmethoxymethylene)chromium(0) (21). A new procedure for the preparation of carbene complexes was developed utilizing dimethyl sulfate as methylating agent. Unlike the benzannulation of the phenyl complex 15, the benzannulation of the naphthylcarbene complex 21 with phenylacetylene gave a side product which resulted from the incorporation of 2 equiv of the alkyne. This side product could be minimized by the proper control of the concentration of the alkyne. The phenol coupling of the 3-phenyl-1-naphthol with ferric chloride gave 2,2‘-diphenyl-[2,2‘-binaphthalene]-4,4‘-diol (38) and with air as oxidant gave the of 3,3‘-diphenyl-[2,2‘-binaphthalene]-1,1‘-diol (39). Oxidative coupling of the 2-phenyl-4-phenanthrol (28) with air gave 2,2‘-diphenyl-[3,3‘-biphenanthrene]-4,4‘-diol (47) (VAPOL), but the same coupling with 2-tert-butyl-4-phenanthrol (34) failed. The 2,2‘-binaphthol 39 was resolved via its cyclic diester with phosphoric acid by salt formation with (−)-brucine, and the 3,3‘-biphenanthrol 47 was resolved via its cyclic deiester with phosphoric acid (49) by salt formation with (−)-cinchonidine. The configuration of (−)-39 was shown to be S from an X-ray analysis of the brucine salt, and the configuration of (+)-47 was shown to be S from an X-ray analysis the amide (S,S)-54 derived from 49 and (S)-α-methylbenzylamine.

This article is available online at http://www.jlr.org Triglycerides (TGs) are the chief route of transport of dietary fat within chylomicrons and VLDLs, as well as the main form of fuel storage in adipose tissue. TGs are synthesized from one glycerol and three FA molecules, which are attached via ester bonds to the hydroxyl groups of the glycerol backbone. Two major diacylglycerol acyltransferase (DGAT) isozymes, DGAT1 and DGAT2, have been identifi ed. Although both enzymes convert diacylglycerol to TG, they do not share similarity in either their nucleotide or amino acid sequences and have most probably arisen by convergent evolution ( 1, 2 ). Although there are some differences in their tissue distributions, both DGAT1 and DGAT2 are highly expressed in organs that synthesize large amounts of TG, such as the liver, adipose tissue, and small intestine ( 3 ).Studies with genetically altered mice, as well as in vivo suppression of DGAT expression, indicate that both DGAT1 and DGAT2 play important roles in TG synthesis. DGAT1 knockout mice (DGAT1 Ϫ / Ϫ ) have reduced tissue TG levels and exhibit increased sensitivity to insulin and leptin ( 4 ). In addition, they are resistant to high-fat dietinduced obesity as a result of an increase in their metabolic rates ( 4 ). In contrast, knockout mice lacking DGAT2 (DGAT2 Ϫ / Ϫ ) are lipopenic and die soon after birth as a result of profound reductions in substrates for energy metabolism and impaired skin permeability ( 5 ). Hepatic suppression of DGAT2 with antisense oligonucleotides (ASOs) reduced hepatic TG content in rodents ( 6, 7 ), and reversed diet-induced hepatic steatosis and insulin resistance Abstract Diacylglycerol acyltransferase (DGAT) catalyzes the fi nal step in triglyceride (TG) synthesis. There are two isoforms, DGAT1 and DGAT2, with distinct protein sequences and potentially different physiological functions. To date, the ability to determine clear functional differences between DGAT1 and DGAT2, especially with respect to hepatic TG synthesis, has been elusive. To dissect the roles of these two key enzymes, we pretreated HepG2 hepatoma cells with

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The first examples of the reactions of Fischer carbene complexes with 1,3-butadiynes are reported. These reactions are of interest since they provide new methods for the synthesis of acetylenic substituted arenes and also for the synthesis of biaryls. The reactions of the complexes (CO)5CrC(OR1)R2 [R1 = Me, n-Bu; R2 = phenyl, 1-naphthyl, 1-cyclohexenyl] were investigated with the conjugated diynes R3C⋮CC⋮CR3 [R3 = t-Bu, i-Pr, Ph]. All of the carbene complexes will react with 1 equiv of the diyne to give good yields of acetylenic arenes 5, 19, and 23, each with high selectivity for the regioisomer in which the substituent R3 on the diyne is incorporated adjacent to the phenol function. The reactions of the alkynylarenes 5, 19, and 23 with a second equivalent of carbene complexes, 4, 16, and 22, respectively, generate the bis-phenols 26, 31, and 33, with varying amounts of five-membered-ring annulated compounds as side products. These side products are not seen with the cyclohexenyl complex 22 and can be minimized to some extent for the phenyl complex 4a by proper control of the concentration and the temperature. Attempts to carry out benzannulations of both of the acetylenic functions in the 1,3-diyne concurrently by employing 2 equiv of the carbene complex were not successful, and this is suspected to be due to the presence of a chromium tricarbonyl group on the newly formed arene ring after the first benzannulation, such as in complex 34. The concurrent double benzannulation of a diyne can be achieved in an intramolecular fashion with the bis-carbene complex 39. The intramolecular process leads to a reversal in the regiochemistry of the second benzannulation producing the C 2-symmetrical 2,2‘-binaphthol 40 from the reaction of complex 39 with the diyne 8 along with the indenylnaphthalene 41. The reaction of the optically pure bis-carbene complex 44 derived from (2R,3R)-butane-2,3-diol with diyne 8 gives a single diastereomer of the 2,2‘-binaphthol 46. Chemical correlation with the known 2,2‘-binaphthol 51 reveals that the biaryl axis in 46 has an S-configuration, which was predicted from an examination of models.

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