Synthesis and reactivity study of allenylphosphonates and aminoallenylphosphonates

Subtitle:Synthese en reactiviteitsstudie van allenylfosfonaten en aminoallenylfosfonaten

Phosphorus-containing natural products and synthetic compounds with a phosphorus moiety possess important antibiotic, antimalarial and herbicidal properties. They are also being used as plant growth regulators in agrochemistry, as water softening agents in laundry detergents and as flame retardants. Bisphosphonates (e.g. Fosamax by Merck) and nucleoside phosphonates (e.g. Tenofovir, marketed by Gilead Sciences as Viread or as the combinatorial pill Truvada) are used as antiosteoporotic and antiviral drugs, respectively. Molecules also containing a nitrogen atom, aminophosphonates, have demonstrated their therapeutic use as well (e.g. fosinopril, marketed by Bristol-Myers Squibb under the tradename Monopril, an antihypertensive drug). In this research, several strategies for the synthesis and reactivity of a new class of precursors to aminophosphonates, aminoallenylphosphonates, have been explored. This has resulted in the first-ever synthesis of a 3-aminoallenylphosphonate, which has been shown to react with oxygen, nitrogen, phosphorus and carbon nucleophiles. A series of oxygen adducts has been prepared from this precursor, while a handful nucleoside phosphonates have been synthesized and evaluated for their antiviral properties. The developed methodology was also evaluated as a strategy to access B-fosmidomycin derivatives with potential antimalarial activity. Allenylphosphonates, on the other hand, have been used in the preparation of chiral spirocyclic oxaphospholenes. These conformationally restricted, bicylic molecules can be considered as cousins of the priviliged chiral inducer BINOL and are consequently of interest because of their potential chirality-inducing properties in asymmetric transformations. For the first time, six such chiral spirocyclic oxaphospholenes have been isolated.

ISBN:9789463570336

Publication year:2017

Accessibility:Open