Synthesis of (±)-7,8-epoxy-4-basmen-6-one by a transannular cyclization strategy

The first synthesis of the cembranoid natural product (±)-7,8-epoxy-4-basmen-6- one (1) is described. Key steps of the synthetic route include the cationic cyclization of the acid chloride from 15 to provide the macrocycle 16, and the photochemical transannular radical cyclization of the ester 41 to form the tricyclic product 50. Product 50 was transformed into 1 in ten steps. Transition-state molecular modeling studies were found to provide accurate predictions of the structural and stereochemical outcomes of cyclization reactions explored experimentally in the development of the synthetic route to 1. These investigations should prove valuable in the development of transannular cyclization as a strategy for synthetic simplification.

A unified strategy to ent-kauranoid natural products : total syntheses of (–)-maoecrystal Z, (–)-trichorabdal A, and (–)-longikaurin E

The diterpenoid constituents of the Isodon plants have attracted reasearchers interested in both their chemical structures and biological properties for more than a half-century. In recent years, the isolations of new members displaying previously unprecedented ring systems and highly selective biological properties have piqued interest from the synthetic community in this class of natural products.

Reported herein is the first total synthesis of such a recently isolated diterpenoid, (–)-maoecrystal Z. The principal transformations implemented in this synthesis include two highly diastereoselective radical cyclization reactions: a Sm^(II)-mediated reductive cascade cyclization, which forms two rings and establishes four new stereocenters in a single step, and a Ti^(III)-mediated reductive epoxide-acrylate coupling that yields a functionalized spirolactone product, which forms a core bicycle of maoecrystal Z.

The preparation of two additional ent-kauranoid natural products, (–)-trichorabdal A and (–)-longikaurin E, is also described from a derivative of this key spirolactone. These syntheses are additionally enabled by the palladium-mediated oxidative cyclization reaction of a silyl ketene acetal precursor that is used to install the bridgehead all-carbon quaternary stereocenter and bicyclo[3.2.1]octane present in each natural product. These studies have established a synthetic relationship among three architecturally distinct ent-kaurane diterpenoids and have forged a path for the preparation of interesting unnatural ent-kauranoid structural analogs for more thorough biological study.

High fidelity probe and mitigation of mirror thermal fluctuations

Thermal noise arising from mechanical loss in high reflective dielectric coatings is a significant source of noise in precision optical measurements. In particular, Advanced LIGO, a large scale interferometer aiming to observed gravitational wave, is expected to be limited by coating thermal noise in the most sensitive region around 30–300 Hz. Various theoretical calculations for predicting coating Brownian noise have been proposed. However, due to the relatively limited knowledge of the coating material properties, an accurate approximation of the noise cannot be achieved. A testbed that can directly observed coating thermal noise close to Advanced LIGO band will serve as an indispensable tool to verify the calculations, study material properties of the coating, and estimate the detector’s performance.

This dissertation reports a setup that has sensitivity to observe wide band (10Hz to 1kHz) thermal noise from fused silica/tantala coating at room temperature from fixed-spacer Fabry–Perot cavities. Important fundamental noises and technical noises associated with the setup are discussed. The coating loss obtained from the measurement agrees with results reported in the literature. The setup serves as a testbed to study thermal noise in high reflective mirrors from different materials. One example is a heterostructure of Al_xGa_1−xAs (AlGaAs). An optimized design to minimize thermo–optic noise in the coating is proposed and discussed in this work.

Applications of a Concise and General Strategy for the Syntheses of Transtaganolide and Basiliolide Natural Products

Herein are described the total syntheses of all members of the transtaganolide and basiliolide natural product family. Utilitzation of an Ireland–Claisen rearrangement/Diels–Alder cycloaddition cascade (ICR/DA) allowed for rapid assembly of the transtaganolide and basiliolide oxabicyclo[2.2.2]octane core. This methodology is general and was applicable to all members of the natural product family.

A brief introduction outlines all the synthetic progress previously disclosed by Lee, Dudley, and Johansson. This also includes the initial syntheses of transtaganolides C and D, as well as basiliolide B and epi-basiliolide B accomplished by Stoltz in 2011. Lastly, we discuss our racemic synthesis of basililide C and epi-basiliolide C, which utilized an ICR/DA cascade to constuct the oxabicyclo[2.2.2]octane core and formal [5+2] annulation to form the ketene-acetal containing 7-membered C-ring.

Next, we describe a strategy for an asymmetric ICR/DA cascade, by incorporation of a chiral silane directing group. This allowed for enantioselective construction of the C8 all-carbon quaternary center formed in the Ireland–Claisen rearrangement. Furthermore, a single hydride reduction and subsequent translactonization of a C4 methylester bearing oxabicyclo[2.2.2]octane core demonstrated a viable strategy for the desired skeletal rearrangement to obtain pentacyclic transtaganolides A and B. Application of the asymmetric strategy culminated in the total syntheses of (–)-transtaganolide A, (+)-transtaganolide B, (+)-transtaganolide C, and (–)-transtaganolide D. Comparison of the optical rotation data of the synthetically derived transtaganolides to that from the isolated counterparts has overarching biosynthetic implications which are discussed.

Lastly, improvement to the formal [5+2] annulation strategy is described. Negishi cross-coupling of methoxyethynyl zinc chloride using a palladium Xantphos catalyst is optimized for iodo-cyclohexene. Application of this technology to an iodo-pyrone geranyl ester allowed for formation and isolation of the eneyne product. Hydration of the enenye product forms natural metabolite basiliopyrone. Furthermore, the eneyne product can undergo an ICR/DA cascade and form transtaganolides C and D in a single step from an achiral monocyclic precursor.