The best way to measure whole body production of the locally acting hormone prostaglandin E 2 (PG... more The best way to measure whole body production of the locally acting hormone prostaglandin E 2 (PGE 2) is to assess the accumulation of the major urinary metabolite, PGE 2 U M. A practical preparation of this delicate diacid is described. This synthetic PGE 2 U M will enable production of the antibodies that will be used to quantify this key metabolite.
Advances in Experimental Medicine and Biology, 2002
1. Adv Exp Med Biol. 2002;507:537-41. Enzyme immunoassays for 15-F2T isoprostane-M, an urinary bi... more 1. Adv Exp Med Biol. 2002;507:537-41. Enzyme immunoassays for 15-F2T isoprostane-M, an urinary biomarker for oxidant stress. Sasaki DM, Yuan Y, Gikas K, Kanai K, Taber D, Morrow JD, Roberts LJ 2nd, Callewaert DM. ...
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are
Reaction of Rh2(S)-PTPA4 with the (R)-citronellol-derived alpha-diazo-beta-ketoester 1 led to the... more Reaction of Rh2(S)-PTPA4 with the (R)-citronellol-derived alpha-diazo-beta-ketoester 1 led to the formation of cyclic beta-ketoester 2 in 95% yield and 48% diastereomeric excess. The purity of 2 was increased to > 99% de after one crystallization. To demonstrate its utility in steroid total synthesis, the beta-ketoester 2 was carried on to secosteroid (-)-astrogorgiadiol (3), a naturally occurring vitamin D analogue with antiproliferative properties.
1,6-and 1,7-enynes are efficiently cyclized to bicyclic metallacyclopentenes with titanocene or z... more 1,6-and 1,7-enynes are efficiently cyclized to bicyclic metallacyclopentenes with titanocene or zirconocene reagents which are easily generated in situ. The metallacycles can be hydrolyzed to release the alkylidenecycloalkane or can be metathesized with main group halides such as SzCl2, SeZCl2, or Ph2SnCI2 to give heterocycles. The zirconium-mediated reaction is more effective for sterically demanding cases. The alkylidene moiety is introduced with 100% stereoselectivity for the &diastereomer; this provides an excellent starting place for the elaboration of chiral side chains as illustrated by a formal synthesis of the ant pheromone invictolide. The cyclization is compatible with alkyl and silyl ether functionality. Sugar enynes, efficiently synthesized from readily available sugar lactones, undergo stereospecific cyclization to highly functional, enantiomerically pure carbocycles. 'Contribution No. 4698. Table I. GLC Yield (%) of Cycloalkanes from Enynes (eq 3)' reagent/enyne 1-octen-6-yne (%) 1-nonen-7-yne (%) Cp2TiClz/PMePhz/Na(Hg) 80 91 Cp2ZrClz/Mg(Hg) 60 51 Cp2ZrCI2/2BuLi 82 89 ' See Experimental Section for detailed reaction conditions. and amalgamated magnesium metal. Of particular interest is the use of this reagent by Negishi et al. to effect the Pauson-Khand type carbonylation of C-silylated enynes to c y c l o p e n t e n~n e s .~~~~ Results and Discussion Comparison of Reagents. Initial studies on the cyclization of the simple enynes 1-octen-6-yne and 1-nonen-7-yne (eq 3) are summarized in Table I. Metallocenes were generated in situ by using the optimized reagent systems developed in our studies on diyne cy~lization.~ Cyclization of either substrate in eq 3 with 1) "Cp2M" CH, = CH (CH,),C=CCH,-F
A Veratrum piperidine chiron was prepared over 11 steps (7.9% yield) from (−)-citronellal. Three ... more A Veratrum piperidine chiron was prepared over 11 steps (7.9% yield) from (−)-citronellal. Three methods for the installation of the propargylic sidechain onto a cyclic enamide are presented.
Cycloalkanones are easily converted into aryl-substituted cyclic alkenes by the addition of an ar... more Cycloalkanones are easily converted into aryl-substituted cyclic alkenes by the addition of an aryl Grignard reagent followed by dehydration. These alkenes are good substrates for asymmetric epoxidation. We have found that the addition of allylic and benzylic Grignard reagents can occur preferentially at the benzylic position of the derived epoxides, to give the quaternary stereogenic center. This approach led to a short synthesis of the nanomolar serotonin re-uptake inhibitor (−)mesembrine.
The first total synthesis of (-)-calicoferol B (III) is described. The cyclozirconation product I... more The first total synthesis of (-)-calicoferol B (III) is described. The cyclozirconation product I, prepared in enantiomerically pure form, was converted into the CD ring chiron II. This was coupled with the aromatic A-ring, and then the side chain was constructed with control of relative and absolute configuration to complete the total synthesis of III. The first total synthesis of (-)-calicoferol B (1) is described. The cyclozirconation product 8, prepared in enantiomerically pure form, was converted into the CD ring chiron 6. This was coupled with the aromatic A-ring, and then the side chain was constructed with control of relative and absolute configuration to complete the total synthesis of 1.
The first enantioselective synthesis of a chamigrane sesquiterpene, (+)-majusculone, has been com... more The first enantioselective synthesis of a chamigrane sesquiterpene, (+)-majusculone, has been completed. The quaternary center was generated asymmetrically by alkylidene carbene insertion, with retention of absolute configuration, from a diastereomerically pure ketal. [email protected]. Supporting Information Available: General experimental procedures, preparation of 11, procedure for racemization, procedure for KHMDS preparation, x-ray crystal for ketal 6 and 1 H and 13 C NMR spectra for all new compounds and (+)-majusculone 3. This material is available free of charge via the Internet at http://pubs.acs.org.
A stereodivergent total synthesis of the Δ 13-9-isofurans has been developed. The four core subst... more A stereodivergent total synthesis of the Δ 13-9-isofurans has been developed. The four core substituted tetrahydrofurans were prepared by the Sharpless asymmetric epoxidation and Sharpless asymmetric dihydroxylation followed by cascade cyclization. The relative configuration at C-8 was inverted by oxidation followed by immediate L-selectride reduction. The relative configuration of the C-15 diastereomers were assigned by (S)-Binol/LAH/EtOH reduction of the corresponding enone. This synthesis of the Δ 13-9-isofurans will provide sufficient material for further investigation of their biological activity. [email protected]. Supporting Information Available. General experimental procedures, experimental procedures and spectra for all new compounds, and details of the x-ray structural analysis of 11a. This material is available free of charge via the Internet at http://pubs.acs.org.
The enantiomerically-pure 5/5-spiroketal required for the synthesis of the ritterazines has been ... more The enantiomerically-pure 5/5-spiroketal required for the synthesis of the ritterazines has been prepared with high diastereocontrol by ring closure followed by equilibration.
Isofurans (IsoF's) are a new class of human arachidonic acid oxidation products. They are produce... more Isofurans (IsoF's) are a new class of human arachidonic acid oxidation products. They are produced in vivo by a free radical mechanism, independent of the cyclooxygenase enzymes. These new compounds are available from natural sources only in microgram quantities as mixtures. The enantioselective preparation of two enediol isofurans, 15-epi-ent-SC-∆ 13-8-IsoF and ent-SC-∆ 13-8-IsoF, is described. A key transformation in the synthesis is the selective cascade cyclization of a diol epoxide benzenesulfonate to give the substituted tetrahydrofuran skeleton of the isofurans. This synthesis will make these metabolites available for physiological evaluation.
The best way to measure whole body production of the locally acting hormone prostaglandin E 2 (PG... more The best way to measure whole body production of the locally acting hormone prostaglandin E 2 (PGE 2) is to assess the accumulation of the major urinary metabolite, PGE 2 U M. A practical preparation of this delicate diacid is described. This synthetic PGE 2 U M will enable production of the antibodies that will be used to quantify this key metabolite.
Advances in Experimental Medicine and Biology, 2002
1. Adv Exp Med Biol. 2002;507:537-41. Enzyme immunoassays for 15-F2T isoprostane-M, an urinary bi... more 1. Adv Exp Med Biol. 2002;507:537-41. Enzyme immunoassays for 15-F2T isoprostane-M, an urinary biomarker for oxidant stress. Sasaki DM, Yuan Y, Gikas K, Kanai K, Taber D, Morrow JD, Roberts LJ 2nd, Callewaert DM. ...
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are
Reaction of Rh2(S)-PTPA4 with the (R)-citronellol-derived alpha-diazo-beta-ketoester 1 led to the... more Reaction of Rh2(S)-PTPA4 with the (R)-citronellol-derived alpha-diazo-beta-ketoester 1 led to the formation of cyclic beta-ketoester 2 in 95% yield and 48% diastereomeric excess. The purity of 2 was increased to > 99% de after one crystallization. To demonstrate its utility in steroid total synthesis, the beta-ketoester 2 was carried on to secosteroid (-)-astrogorgiadiol (3), a naturally occurring vitamin D analogue with antiproliferative properties.
1,6-and 1,7-enynes are efficiently cyclized to bicyclic metallacyclopentenes with titanocene or z... more 1,6-and 1,7-enynes are efficiently cyclized to bicyclic metallacyclopentenes with titanocene or zirconocene reagents which are easily generated in situ. The metallacycles can be hydrolyzed to release the alkylidenecycloalkane or can be metathesized with main group halides such as SzCl2, SeZCl2, or Ph2SnCI2 to give heterocycles. The zirconium-mediated reaction is more effective for sterically demanding cases. The alkylidene moiety is introduced with 100% stereoselectivity for the &diastereomer; this provides an excellent starting place for the elaboration of chiral side chains as illustrated by a formal synthesis of the ant pheromone invictolide. The cyclization is compatible with alkyl and silyl ether functionality. Sugar enynes, efficiently synthesized from readily available sugar lactones, undergo stereospecific cyclization to highly functional, enantiomerically pure carbocycles. 'Contribution No. 4698. Table I. GLC Yield (%) of Cycloalkanes from Enynes (eq 3)' reagent/enyne 1-octen-6-yne (%) 1-nonen-7-yne (%) Cp2TiClz/PMePhz/Na(Hg) 80 91 Cp2ZrClz/Mg(Hg) 60 51 Cp2ZrCI2/2BuLi 82 89 ' See Experimental Section for detailed reaction conditions. and amalgamated magnesium metal. Of particular interest is the use of this reagent by Negishi et al. to effect the Pauson-Khand type carbonylation of C-silylated enynes to c y c l o p e n t e n~n e s .~~~~ Results and Discussion Comparison of Reagents. Initial studies on the cyclization of the simple enynes 1-octen-6-yne and 1-nonen-7-yne (eq 3) are summarized in Table I. Metallocenes were generated in situ by using the optimized reagent systems developed in our studies on diyne cy~lization.~ Cyclization of either substrate in eq 3 with 1) "Cp2M" CH, = CH (CH,),C=CCH,-F
A Veratrum piperidine chiron was prepared over 11 steps (7.9% yield) from (−)-citronellal. Three ... more A Veratrum piperidine chiron was prepared over 11 steps (7.9% yield) from (−)-citronellal. Three methods for the installation of the propargylic sidechain onto a cyclic enamide are presented.
Cycloalkanones are easily converted into aryl-substituted cyclic alkenes by the addition of an ar... more Cycloalkanones are easily converted into aryl-substituted cyclic alkenes by the addition of an aryl Grignard reagent followed by dehydration. These alkenes are good substrates for asymmetric epoxidation. We have found that the addition of allylic and benzylic Grignard reagents can occur preferentially at the benzylic position of the derived epoxides, to give the quaternary stereogenic center. This approach led to a short synthesis of the nanomolar serotonin re-uptake inhibitor (−)mesembrine.
The first total synthesis of (-)-calicoferol B (III) is described. The cyclozirconation product I... more The first total synthesis of (-)-calicoferol B (III) is described. The cyclozirconation product I, prepared in enantiomerically pure form, was converted into the CD ring chiron II. This was coupled with the aromatic A-ring, and then the side chain was constructed with control of relative and absolute configuration to complete the total synthesis of III. The first total synthesis of (-)-calicoferol B (1) is described. The cyclozirconation product 8, prepared in enantiomerically pure form, was converted into the CD ring chiron 6. This was coupled with the aromatic A-ring, and then the side chain was constructed with control of relative and absolute configuration to complete the total synthesis of 1.
The first enantioselective synthesis of a chamigrane sesquiterpene, (+)-majusculone, has been com... more The first enantioselective synthesis of a chamigrane sesquiterpene, (+)-majusculone, has been completed. The quaternary center was generated asymmetrically by alkylidene carbene insertion, with retention of absolute configuration, from a diastereomerically pure ketal. [email protected]. Supporting Information Available: General experimental procedures, preparation of 11, procedure for racemization, procedure for KHMDS preparation, x-ray crystal for ketal 6 and 1 H and 13 C NMR spectra for all new compounds and (+)-majusculone 3. This material is available free of charge via the Internet at http://pubs.acs.org.
A stereodivergent total synthesis of the Δ 13-9-isofurans has been developed. The four core subst... more A stereodivergent total synthesis of the Δ 13-9-isofurans has been developed. The four core substituted tetrahydrofurans were prepared by the Sharpless asymmetric epoxidation and Sharpless asymmetric dihydroxylation followed by cascade cyclization. The relative configuration at C-8 was inverted by oxidation followed by immediate L-selectride reduction. The relative configuration of the C-15 diastereomers were assigned by (S)-Binol/LAH/EtOH reduction of the corresponding enone. This synthesis of the Δ 13-9-isofurans will provide sufficient material for further investigation of their biological activity. [email protected]. Supporting Information Available. General experimental procedures, experimental procedures and spectra for all new compounds, and details of the x-ray structural analysis of 11a. This material is available free of charge via the Internet at http://pubs.acs.org.
The enantiomerically-pure 5/5-spiroketal required for the synthesis of the ritterazines has been ... more The enantiomerically-pure 5/5-spiroketal required for the synthesis of the ritterazines has been prepared with high diastereocontrol by ring closure followed by equilibration.
Isofurans (IsoF's) are a new class of human arachidonic acid oxidation products. They are produce... more Isofurans (IsoF's) are a new class of human arachidonic acid oxidation products. They are produced in vivo by a free radical mechanism, independent of the cyclooxygenase enzymes. These new compounds are available from natural sources only in microgram quantities as mixtures. The enantioselective preparation of two enediol isofurans, 15-epi-ent-SC-∆ 13-8-IsoF and ent-SC-∆ 13-8-IsoF, is described. A key transformation in the synthesis is the selective cascade cyclization of a diol epoxide benzenesulfonate to give the substituted tetrahydrofuran skeleton of the isofurans. This synthesis will make these metabolites available for physiological evaluation.
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