Chemoenzymatic Total Synthesis of Morphine alkaloids: Synthesis of Dihydrocodeine and Hydrocodone via a Double Claisen Strategy and ent-Hydromorphone via an Oxidative Dearomatization/intramolecular [4+2] Cycloaddition

This thesis describes the chemoenzymatic synthesis of three morphine alkaloids. The total synthesis of dihydrocodeine and hydrocodone was accomplished starting from bromobenzene in 16 and 17 steps, respectively. The key steps included a microbial oxidation of bromobenzene by E. coli JM109 (pDTG601A), a Kazmaier-Claisen rearrangement of glycinate ester to generate C-9 and C-14 stereo centers, a Johnson-Claisen rearrangement to set the C-13 quaternary center, and a C-10/C-11 ring closure via a Friedel-Crafts reaction. In addition, the total synthesis of ent-hydromorphone starting from β-bromoethylbenzene in 12 steps is also described. The key reactions included the enzymatic dihydroxylation of β-bromoethylbenzene to the corresponding cis-cyclohexadienediol, a Mitsunobu reaction, and an oxidative dearomatization followed by an intramolecular [4+2] cycloaddition.

Letter - E.C. Schmon to Arthur A. Schmon, 13 July 1917

The letter describes a party with family at the Pell Tree Inn where they had dinner and dancing. She also mentions that Arthur was made an instructor of topography and may soon do his examinations for second lieutenant.

Letter - E.C. Schmon to Arthur A. Schmon, 13 May 1919

The letter describes a day Eleanore Celeste spent downtown and many friends she ran into during her outing. She then mentions an article she read that states most troops will be out of France by July 1st. This letter is labelled number 278.

Letter - E.C. Schmon to Arthur A. Schmon, 13 April 1916

The letter states that they will see one another on the nineteenth and Eleanore Celeste is excited for the date to arrive. She also mentions some volunteer work "tagging" for donations for the "benefit of war sufferers". She also attends a concert of Columbia University given at Carnegie Hall.

Letter - E.C. Schmon to Arthur A. Schmon, 13 November 1919

Eleanore Celeste is on her way to Mother Schmon's. She has been shopping and to see friends. She will leave for Shelter Bay in a month or so. The letter is labelled number 33 & 34.

Letter - E.C. Schmon to Arthur A. Schmon, 13 November 1918

Eleanore Celeste is teaching at Lafayette Street School. She states that she likes "this school better than any I've substituted in." She writes about a boy who could not attend school because he had no shoes and the family was living in terrible conditions with barely anything to eat. She has also read some articles about men returning from France and she is hoping that Arthur will return soon. The letter is labelled number 189.

Letter - E.C. Schmon to Arthur A. Schmon, 13 July 1918

Eleanore Celeste discusses going to the theatre alone and remarks "these war times are making girls independent". She also mentions her studies and how much she enjoys learning. She has enclosed an article titled "Heroes of our Army Parade in Paris". The letter is labelled number 127.

Letter - E.C. Schmon to Arthur A. Schmon, 13 April 1917

Eleanore Celeste mentions she went to see the film "The Matrimaniac" starring Douglas Fairbanks. She hopes to travel to Princeton in a week or so to visit Arthur. He is studying for exams.