Enantiomerically pure acetals in organic synthesis. 3. A synthesis of (R)-mevalonic acid lactone

1991 ◽  
Vol 56 (2) ◽  
pp. 885-888 ◽  
Author(s):  
Eugene A. Mash ◽  
Jeffrey B. Arterburn
Keyword(s):  
Organic Synthesis ◽  
Mevalonic Acid ◽  
Enantiomerically Pure ◽  
Acid Lactone

scholarly journals Incorporation of dl-[2−14C]mevalonic acid lactone into β-carotene and the phytol side chain of chlorophyll in cotyledons of four species of pine seedlings

1967 ◽  
Vol 105 (1) ◽  
pp. 89-92 ◽  
Author(s):  
S. Wieckowski ◽  
T W Goodwin
Keyword(s):  
Mevalonic Acid ◽  
Side Chain ◽  
Pinus Silvestris ◽  
Pine Seedlings ◽  
Acid Lactone ◽  
Β Carotene

1. The incorporation of dl-[2−14C]mevalonic acid lactone into β-carotene and the phytol side chain of chlorophyll has been investigated in cotyledons of four species of pine seedlings (Pinus silvestris, P. contorta, P. radiata and P. jeffrei) grown in darkness and in light. 2. The relative incorporation of label into β-carotene and the phytol side chain of chlorophyll is similar to that observed in experiments on monocotyledons and dicotyledons. 3. The relative incorporation of 14CO2 into β-carotene and phytol is much higher than the incorporation of [2−14C]mevalonic acid.

Enzymes in organic synthesis. 32. Stereospecific horse liver alcohol dehydrogenase-catalyzed oxidations of exo- and endo-oxabicyclic meso diols

1984 ◽  
Vol 62 (11) ◽  
pp. 2578-2582 ◽  
Author(s):  
J. Bryan Jones ◽  
Christopher J. Francis
Keyword(s):  
Alcohol Dehydrogenase ◽  
Organic Synthesis ◽  
Horse Liver Alcohol Dehydrogenase ◽  
Preparative Scale ◽  
Enantiomerically Pure ◽  
Liver Alcohol Dehydrogenase ◽  
Horse Liver ◽  
One Step ◽  
Catalyzed Oxidation ◽  
Enzymes In Organic Synthesis

Preparative-scale horse liver alcohol dehydrogenase-catalyzed oxidation of mesoexo- and endo-7-oxabicyclo[2.2.1]heptane diols provides a direct one-step route to enantiomerically pure chiral γ-lactones of the oxabicyclic series.

The Evans Synthesis of (–)-Nakadomarin A

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Organic Synthesis ◽  
Allyl Alcohol ◽  
First Generation ◽  
Direct Conversion ◽  
Heck Coupling ◽  
Ring Closing Metathesis ◽  
Selective Activation ◽  
Enantiomerically Pure ◽  
Ru Catalyst ◽  
Nakadomarin A

(–)-Nakadomarin A (4), isolated from the marine sponge Amphimedon sp. off the coast of Okinawa, shows interesting cytotoxic and antibacterial activity. David A. Evans of Harvard University prepared (J. Am. Chem. Soc. 2013, 135, 9338) 4 by coupling the enantiomerically pure lactam 2 with the prochiral lactam 1. The preparation of 1 began with the aldehyde 5. Following the Comins protocol, addition of lithio morpholine to the carbonyl gave an intermediate that could be metalated and iodinated. Protection of the aldehyde followed by Heck coupling with allyl alcohol gave the aldehyde 7. Addition of the phosphorane derived from 8 followed by deprotection gave 9 with the expected Z selectivity. Addition of the phosphonate 10 was also Z selective, leading to the lactam 1. The preparation of 2 began with the enantiomerically pure imine 12. The addition of 13 was highly diastereoselective, setting the absolute configuration of 15. Alkylation with the iodide 16 delivered 17, which was closed to 2 under conditions of kinetic ring-closing metathesis, using the Grubbs first generation Ru catalyst. The condensation of 1 with 2 gave both of the diastereomeric products, with a 9:1 preference for the desired 3. Experimentally, acid catalysis alone did not effect cyclization, suggesting that the cyclization is proceeding via silylated intermediates. The diastereoselectivity can be rationalized by a preferred extended transition state for the intramolecular Michael addition. Selective activation of 3 followed by reduction gave 18, which underwent Bischler-Napieralski cyclization to give an intermediate that could be reduced to (–)-nakadomarin A (4). It was later found that exposure of 3 to Tf2O and 19 followed by the addition of Redal gave direct conversion to 4. It is instructive to compare this work to the two previous syntheses of 4 that we have highlighted, by Dixon (OHL May 3, 2010) and by Funk (OHL July 4, 2011). Together, these three independent approaches to 4 showcase the variety and dexterity of current organic synthesis.

The Sato/Chida Synthesis of Paclitaxel (Taxol®)

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Organic Synthesis ◽  
Conjugate Addition ◽  
Cyclic Carbonate ◽  
Membered Ring ◽  
Standard Protocol ◽  
Protecting Group ◽  
Enantiomerically Pure ◽  
Facial Selectivity ◽  
Starting Point ◽  
Nabh4 Reduction

Paclitaxel (Taxol®) 3 is widely used in the clinical treatment of a variety of cancers. Takaaki Sato and Noritaka Chida of Keio University envisioned (Org. Lett. 2015, 17, 2570, 2574) establishing the central eight-membered ring of 3 by the SmI2-mediated cyclization of 1 to 2. The starting point for the synthesis was the enantiomerically-pure enone 5, pre­pared from the carbohydrate precursor 4. Conjugate addition to 5 proceeded anti to the benzyloxy substituent to give, after trapping with formaldehyde and protection, the ketone 6. Reduction and protection followed by hydroboration led to 7, that was, after protection and deprotection, oxidized to 8. The second ring of 3 was added in the form of the alkenyl lithium derivative 9, prepared from the trisylhydrazone of the corresponding ketone. Hydroxyl-directed epoxidation of 10 proceeded with high facial selectivity, leading, after reduction and protection, to the cyclic carbonate 11. Allylic oxidation converted the alkene into the enone, while at the same time oxidizing the benzyl protecting group to the ben­zoate, to give 12. Reduction of the ketone 12 led to a mixture of diastereomers. In practice, only one of the diastereomers of 1 cyclized cleanly to 2, as illustrated, so the undesired diastereomer from the NaBH4 reduction was oxidized back to the enone for recycling. For convenience, only one of the diastereomers of 2 was carried forward. To establish the tetrasubstituted alkene of 3, the alkene of 2 was converted to the cis diol and on to the bis xanthate 13. Warming to 50°C led to the desired tet­rasubstituted alkene, sparing the oxygenation that is eventually required for 3. For convenience, to intercept 16, the intermediate in the Takahashi total synthesis, both xanthates were eliminated to give 14. Hydrogenation removed the disubsti­tuted alkene, and also deprotected the benzyl ether. Oxidation followed by Peterson alkene formation led to 15, that was carried on to the Takahashi intermediate 16 using the now-standard protocol for oxetane construction. It is a measure of the strength of the science of organic synthesis that Masahisa Nakada of Waseda University also reported (Chem. Eur. J. 2015, 21, 355) an elegant synthesis of 3 (not illustrated).

Sterol Synthesis in Human Endothelial Cells

1975 ◽  
Author(s):  
S. A. Evensen ◽  
T. Henriksen
Keyword(s):  
Endothelial Cells ◽  
Mevalonic Acid ◽  
Acid Synthesis ◽  
Sterol Fraction ◽  
Sterol Synthesis ◽  
Human Endothelial Cells ◽  
Intermediary Product ◽  
Acid Lactone ◽  
Umbilical Cords ◽  
Progressive Accumulation

Endothelial cells were isolated by collagenase digestion of the intima of the vein of umbilical cords and grown in medium 199 or RPMI 1640 supplemented with 20% FCS. After 3–5 days in primary culture fresh medium was added containing either sodium acetate-2-14C or mevalonic acid lactone-2-14C. Following further 24, 48 or 96 h incubation the harvested cells and media were extracted according to Folch and separated on TLC. About 35% of the total cellular radioactivity accumulated in the sterol fraction after 48 h incubation with labelled acetate. Delipidation of the medium resulted in markedly increased incorporation. Incorporation of mevalonic acid into cellular sterols was maximal at 48 h, and larger in RPMI 1640 than in medium 199. In the medium a progressive accumulation of labelled sterols with time was observed. Approximately 20% of the cellular radioactivity was found in the FFA fraction and was saponifiable. Whether this finding represents fatty acid synthesis from mevalonic acid or an intermediary product in sterol synthesis has not yet been clarified.

Enzymes in organic synthesis. 26.Synthesis of enantiomerically pure grandisol from an enzyme-generated chiral synthon

1982 ◽  
Vol 60 (15) ◽  
pp. 2007-2011 ◽  
Author(s):  
J. Bryan Jones ◽  
Mark A. W. Finch ◽  
Ignac J. Jakovac
Keyword(s):  
Organic Synthesis ◽  
Pure Material ◽  
Enantiomerically Pure ◽  
Optically Pure ◽  
Enzymes In Organic Synthesis ◽  
Chiral Synthon

The synthesis of enantiomerically pure (+)-grandisol has been achieved from an enzymically generated chiral synthon. The synthesis is an efficient one, the yield of optically pure material being 12% up to the penultimate step and 3% overall.

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