Studies toward a total synthesis of taxol : the intramolecular Diels-Alder approach / Samit Kumar Bhattacharya.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Bhattacharya, Samit Kumar.

Contributor:

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Chemistry.

Chemistry--Penn dissertations.

Local Subjects:

Penn dissertations--Chemistry.

Chemistry--Penn dissertations.

Physical Description:

2 volumes (xxxii, 463 pages) : illustrations ; 29 cm

Production:

1996.

Summary:

This dissertation describes strategies toward synthesis of taxol 1.1 and taxane analogs.*

The chemistry discussed in this treatise has led to the development of an exceedingly economical synthesis of the A-ring synthon (4.86) of taxol and other taxanes.*

The key intermediate 4.86 has been converted to a diol which possesses the critical C-13 and C-2 oxygenation in place in the desired stereochemistry. After a number of unsuccessful strategies to form the B-ring by direct closure, the diol 4.100 was elaborated to an Intramolecular Diels-Alder substrate 4.126.*

The Intramolecular Diels-Alder reaction was utilized to furnish excellent yields of the tricyclic taxane framework albeit with the undesired cis-$\alpha$ BC ring fusion. The major Diels-Alder adduct 4.128 has been converted to a taxinine (6.1) like analog 5.92a through a short sequence of cyclopropanation and treatment with Zeise's dimer.* The allylic alcohol could not be hydroxylated at the terminal olefin and this has been rationalized as due to the steric abutment by the C-2 methoxy group. The alcohol 5.92a has been converted to an epoxy alcohol 5.99 but could not be converted to the desired oxetane of taxanes. The steric hindrance of the C-2 methoxy group has again been identified as responsible for preventing the epoxide opening.* Both the allylic alcohol 5.92a and the epoxy alcohol 5.99 are viable candidates for connecting to the side-chain of taxol and submitting for biological testing.

Based on the chemistry developed in this treatise, a similar Diels-Alder reaction on the C-1 oxygenated series has been successfully carried out in our laboratories. Together with the possibility of incorporation of a second generation diene (being developed in our laboratories), this has led to the evolution of a future strategy which addresses the C-8 methyl introduction, the desired trans BC ring junction and an eventual oxetane synthesis. ftn*Please refer to the dissertation for diagrams.

Notes:

Thesis (Ph.D. in Chemistry) -- University of Pennsylvania, 1996.

Includes bibliographical references and index.

Local Notes:

University Microfilms order no.: 97-12889.

OCLC:

187470453