Douglass F. Taber

A nomenclature system for the isoprostanes

In 1990, prostaglandin (PG) F2-like compounds were discovered to be produced in abundance in vivo by a free radical mechanism independent of the cyclooxygenase enzyme. Because these compounds are isomeric to cyclooxygenase-derived PGF2 alpha, they were termed F2-isoprostanes (F2-IsoPs). Subsequently, it was also demonstrated that PGD2-like compounds (D2-IsoPs) and PGE2-like compounds (E2-IsoPs) are also produced in vivo as products of this pathway. Four different regioisomers of each of these classes of IsoPs are formed, each of which can be comprised of eight racemic diastereomers. Thus, 64 different F2-IsoPs, E2-IsoPs, and D2-IsoPs can be formed. Interest in these molecules stems not only from the fact that quantification of IsoPs can provide a valuable index of free radical-induced lipid peroxidation in vivo but also from the fact that it has been shown that these compounds are capable of exerting potent biological activity. Because of this potential for exerting biological activity, the chemical syntheses of various IsoP compounds for biological testing has been initiated. As a result, a need for a systematic nomenclature for these compounds has evolved. A facile nomenclature that will allow rational differentiation and designation of each of the isomeric structures comprising the family of IsoPs is presented.

Intramolecular Diels-Alder and Alder Ene Reactions

1. The Intramolecular Diels-Alder Reaction: Variations and Scope.- I. Introduction.- II. Range and Preparation of Dienes.- III. Range and Preparation of Dienophiles.- IV. Heterodienes and Dienophiles.- V. Catalysis of the Reaction.- VI. Conclusion.- VII. References.- 2. The Intramolecular Diels-Alder Reaction: Reactivity and Stereocontrol.- I. Introduction.- II. Factors Influencing the Rate of Cyclization.- 1. Influence of Dienophile Substitution on the Rate of Cyclization.- 2. Influence of Diene Substitution on the Rate of Cyclization.- 3. Influence of the Elements Bridging the Diene and Dienophile on the Rate of Cyclization.- a) Effect of Ring Size.- b) Effect of Buttressing.- c) Effect of Heteroatoms in the Bridge on the Rate of Cyclization.- III. Factors Influencing the Stereochemical Outcome of the Cyclization.- 1. Triene Geometry.- 2. Cis vs. Trans Ring Fusion.- a) Preference for an Endo Transition State.- b) Influence of Diene Substitution on the Geometry of Ring Fusion.- c) Influence of the Bridge Between the Diene and the Dienophile on the Geometry of Ring Fusion.- 3. Diastereomeric Control by Remote Chiral Centers.- a) Diastereomeric Control by a Rigid Skew in the Bridge.- b) Diastereomeric Control by a Substituent on the Bridge.- c) Diastereomeric Control by an Alkoxy Substituent on the Bridge.- d) Diastereomeric Control by Chiral Centers not Included in the Bridge.- IV. Summary.- V. References.- 3. The Intramolecular Alder Ene Reaction.- I. Introduction.- II. Reactivity of Ene Acceptors.- 1. Unactivated Olefins.- 2. Activated Olefins.- 3. Acetylenes.- III. Reactivity of Ene Donors.- 1. Unactivated Donors.- 2. Speculations on Activated Donors.- IV. Steric and Stereoelectronic Control Elements in the Intramolecular Ene Reaction.- 1. Cis vs. Trans Relationship of the Two Interacting Side Chains.- 2. Diastereometric Control by Substituents on the Bridge Between the Ene Donor and the Ene Acceptor.- 3. Diastereomeric Control of Carbon-Carbon Bond Formation by Other Remote Substituents.- V. Directions for the Future.- VI. Tables.- 1. Carbocyclic, Type I, Unactivated Olefin Acceptor.- 2. Carbocyclic, Type I, Activated Olefm Acceptor.- 3. Carbocyclic, Type I, Acetylene Acceptor.- 4. Heterocyclic, Type I, Unactivated Olefin Acceptor.- 5. Heterocyclic, Type I, Activated Olefin Acceptor.- 6. Heterocyclic, Type I, Acetylene Acceptor.- 7. Type II.- 8. Type III.- 9. Organometallic.- VII. References.

Enantioselective reduction of β-keto esters

Abstract Highly enantioselective reduction of β-keto esters with BINAP-Ru catalyst can be effected at 50 psig H2 and 80°, using a Parr shaker. A simplified preparation of the BINAP-Ru catalyst is reported. Highly enantioselective reduction of β-keto esters with BINAP-Ru catalyst can be effected at 50 psig H2 and 80°, using a Parr shaker. A simplified preparation of the BINAP·Ru catalyst is reported.

Synthesis of (−)-Astrogorgiadiol

Astrogorgiadiol is a naturally occurring Vitamin D analogue that, in cell culture, downregulates the production of the cytokine osteopontin (OPN). OPN has been implicated in virulent asthma, and OPN knockout mice do not develop osteoporosis. As we have pursued whole animal studies with astrogorgiadiol, we have increased the scale of the synthesis. We report an improved preparation of the A-ring synthon and the scale-up of the diasteromerically pure D-ring/sidechain chiron.

Diastereoselection in rhodium-mediated intramolecular C-H insertion: preparation of a trans-3,4 dialkyl cyclopentane

Abstract Transition state analysis suggests that substantial 1,2 asymmetric induction could be observed in the course of rhodium-mediated intramolecular C-H insertion. This analysis successfully predicts predominant formation of the trans 3,4-dialkyl cyclopentane when an α-diazo β-ketoester having a δ-phenyl substituent is cyclized.

Convenient Access to Bicyclic and Tricyclic Diazenes

Heating the tosylhydrazone of an omega-alkenyl ketone or aldehyde to reflux in toluene in the presence of K(2)CO(3) delivered the bicyclic diazene. Irradiation of the diazene converted it to the cyclopropane. This appears to be a generally useful method for the construction of substituted cyclopentanes and cyclohexanes.

Synthesis of Natural Products By Rhodium‐Mediated Intramolecular C–H Insertion

The strategic advantages of the Rh-mediated intramolecular C–H insertion, which has been used as the key step in several natural product syntheses, are described here. The most recent such synthesis is the elegant route to (+)-morphine shown below.

Synthesis of (‐)‐Hamigeran B

The synthesis of (-)-hamigeran B has been achieved, based on a new approach to cyclopentane construction, the rhodium-mediated intramolecular C-H insertion of alpha-aryl-alpha-diazoketones. The endo-isopropyl group was installed by selective hydrogenation of a cyclopropylidene substituent.

–NH– Termination of the Si(111) Surface by Wet Chemistry

For over a quarter of a century the hydrogen-terminated Si(111) single-crystalline surface has been the gold standard as a starting point for silicon surface modification chemistry. However, creating a well-defined and stable interface based on Si-N bonds has remained elusive. Despite the fact that azides, nitro compounds, and amines do lead to the formation of surface Si-N, each of these modification schemes produces additional carbon- or oxygen-containing functional groups that in turn react with the surface itself, leaving contaminants that affect the interface properties for any further modification protocols. We describe the preparation of a Si(111) surface functionalized predominantly with Si-NH-Si species based on chlorination followed by the room temperature ammonia treatment utilizing NH(3)-saturated tetrahydrofuran (THF). The obtained surface has been characterized by infrared spectroscopy and X-ray photoelectron spectroscopy. This analysis was supplemented with DFT calculations. This newly characterized surface will join the previously established H-Si(111) and Cl-Si(111) surfaces as a general starting point for the preparation of oxygen- and carbon-free interfaces, with numerous potential applications.

Intramolecular [1 + 4 + 1] Cycloaddition: Establishment of the Method

Structurally complex and physiologically active natural products often include bicyclic and polycyclic ring systems having defined relative and absolute configuration. Approaches that allow the construction of more than one carbocyclic ring at a time have proven valuable, in particular those that allow at the same time the control of an array of new stereogenic centers. One of the most general and most widely used protocols has been the intramolecular Diels-Alder [4 + 2] cycloaddition, in which a single stereogenic center between the diene and the dienophile can control the relative and absolute configuration of the product. We report a two-step [1 + 4 + 1] procedure for bicyclic and polycyclic construction, based on the cyclization of an omega-dienyl ketone. This is complementary to, and will likely be as useful as, the intramolecular Diels-Alder cycloaddition.