Polyketide construction via hydrohydroxyalkylation and related alcohol C-H functionalizations: reinventing the chemistry of carbonyl addition.

Despite the longstanding importance of polyketide natural products in human medicine, nearly all commercial polyketide-based drugs are prepared through fermentation or semi-synthesis. The paucity of manufacturing routes involving de novo chemical synthesis reflects the inability of current methods to concisely address the preparation of these complex structures. Direct alcohol C-H bond functionalization via"C-C bond forming transfer hydrogenation" provides a powerful, new means of constructing type I polyketides that bypasses stoichiometric use of chiral auxiliaries, premetallated C-nucleophiles, and discrete alcohol-to-aldehyde redox reactions. Using this emergent technology, total syntheses of 6-deoxyerythronolide B, bryostatin 7, trienomycins A and F, cyanolide A, roxaticin, and formal syntheses of rifamycin S and scytophycin C, were accomplished. These syntheses represent the most concise routes reported to any member of the respective natural product families.

Asymmetric alcohol C-H allylation and syn-crotylation: C9-C20 of tetrafibricin.

The C9-C20 segment of the fibrinogen receptor inhibitor tetrafibricin was prepared in 10 steps (longest linear sequence). Ruthenium catalyzed enantioselective syn-crotylation is used to construct C9-C13. Iridium catalyzed asymmetric alcohol C-H allylation of a commercial malic acid derived alcohol is used to construct C14-C20. Recovery and recycling of the iridium catalyst is described.

[Anesthetic management for gastrectomy in two gastric cancer patients after coronary artery bypass grafting using right gastroepiploic artery].

We report two cases for anesthetic management of gastrectomy for gastric cancer which took place after receiving coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA). The first patient was a 75-year-old man after CABG using the RGEA 14 years before. He was diagnosed with gastric cancer and was scheduled for total gastrectomy. Preoperative coronary angiography (CAG) showed complete occlusion of the right coronary artery (RCA), whereas RGEA was patent. Because percutaneous coronary intervention (PCI) was hard to perform on the occluded RCA, proximal gastrectomy was carried out without lymph node dissection. The surgeons judged the surgery enough for radical treatment. Surgery was accomplished without any problems. The second patient was a 76-year-old man after CABG using the RGEA 15 years before. He was diagnosed with advanced gastric cancer and was scheduled for distal gastrectomy. Preoperative CAG showed the RCA partially occluded and the RGEA remaining patent. He received the scheduled surgery after confirmation of the success of PCI, performed preoperatively for reperfusion of the occluded segments. Although the RGEA was incised during the surgery, gastrectomy was accomplished without any problems in the cardiac function.

Asymmetric aldol reaction of acetaldehyde and isatin derivatives for the total syntheses of ent-convolutamydine E and CPC-1 and a half fragment of madindoline A and B.

The asymmetric aldol reaction of isatin derivatives and acetaldehyde has been developed using 4-hydroxydiarylprolinol as a catalyst, affording the aldol products with high enantioselectivity, these products being key intermediates in the synthesis of 3-hydroxyindole alkaloids. Short syntheses of ent-convolutamydine E and CPC-1 and a half fragment of madindoline A and B have been accomplished.

Asymmetric, catalytic, and direct self-aldol reaction of acetaldehyde catalyzed by diarylprolinol.

An asymmetric, catalytic, and direct self-aldol reaction of acetaldehyde was catalyzed by diarylprolinol in NMP, affording the trimer acetal, which was generated by the reaction of the self-aldol product with another acetaldehyde molecule in a moderate yield with good enantioselectivity. Acetal is the synthetic equivalent of the self-aldol product, which can be converted into other synthetically useful compounds in one pot without compromising the enantioselectivity.

Highly diastereo- and enantioselective direct aldol reactions of aldehydes and ketones catalyzed by siloxyproline in the presence of water.

Proline-based organocatalysts have been developed for a highly enantioselective, direct aldol reaction of aldehydes and ketones in the presence of water. While several surfactant-proline combined catalysts have proved effective, proline derivatives with a hydrophobic moiety such as trans-siloxy-L-proline and cis-siloxy-D-proline, both of which are easily prepared from the same commercially available 4-hydroxy-L-proline, have been found to be the most effective organocatalysts examined in this study, affording the aldol product with excellent diastereo- and enantioselectivities, these two catalysts generating opposite enantiomers. Water affects the selectivity, and poor results are obtained under neat reaction conditions or in dry organic solvents. More than three equivalents of water are required for the best diastereo- and enantioselectivities, while three equivalents is the recommended amount from a synthetic point of view. The reaction proceeds in the organic phase, and also proceeds in the presence of a large amount of water. The large-scale preparation of aldols with the minimal use of an organic solvent, including in the purification step, is described.

Small organic molecule in enantioselective, direct aldol reaction "in water".

A small organic molecule, Pro-NH(2), catalyzing the enantioselective aldol reaction "in water" not merely "in the presence of water" with good enantioselectivity has been discovered for the first time.

Differentiation between intradural and extradural locations of juxta-dural ring aneurysms by using contrast-enhanced 3-dimensional time-of-flight magnetic resonance angiography.

BACKGROUND: Juxta-dural ring aneurysms of the ICA have different clinical outcomes and risks for SAH, which are dependent on their position in the intradural or extradural space. The aim of this study was to reveal the precise location of such aneurysms by using CE-MRA. METHODS: Contrast-enhanced MRA studies were performed in 21 patients with 24 juxta-dural ring aneurysms. The locations were evaluated by source images of CE-MRA and MPR images. We evaluated the accuracy of preoperative MRI findings by comparing imaging results with intraoperative findings in 7 cases. RESULTS: The CS was clearly enhanced in the CE-MRA technique, which allowed the precise identification of these aneurysms as intradural or extradural. Intracavernous aneurysms were diagnosed when the greater hyperintensity of the aneurysm was located within the less hyperintense region of the contrast-enhanced CS. Nine of the cases were diagnosed as intradural aneurysms, and 15 aneurysms were noted as extradural based on the findings of CE-MRA. Surgery was performed in 7 cases, which included 4 intradural and 3 extradural aneurysms, and the preoperative MRI findings corresponded with the intraoperative findings in all cases. CONCLUSION: Contrast-enhanced MRA and MPR are very useful techniques for determining the location of juxta-dural ring aneurysms.

Dry and wet prolines for asymmetric organic solvent-free aldehyde-aldehyde and aldehyde-ketone aldol reactions.

Dry and wet prolines were found to catalyze the direct aldol reactions of aldehyde-aldehyde and aldehyde-ketone, respectively, to afford aldols with excellent diastereo- and enantioselectivities, and an organic solvent-free reaction was realized in some cases.