Biomimetic Total Synthesis Of Securidanes A&B And Studies On The Asymmetric Total Synthesis Of Rubromycins

This thesis specific to the studies on the asymmetric total synthesis of natural products Rubromycins and the biomimetic total synthesis of Securidanes A&B, and the contents could be divided into the following two parts.Chaper 1. The First Biomimetic Total Synthesis of Securidanes A&BIn this chaper, we depicted the isolation, bioactivities and biomimetic total synthesis of Securidanes A&B. The target molecules Securidanes A&B features a triarylmethane skeleton which could be synthesized from secondary benzylic alcohol 1-116 and electron-rich arene 1-118. Accordingly, we first synthesized compounds 1-116 and 1-118 via several steps of simple transformation, then Fe(Cl O4)3?H2O catalyzed Friedel–Crafts type alkylation was used as the key step to constuct the triarylmethane scaffold. The total synthesis of Securidanes A&B were achieved in 5 steps with a groundbreaking 26.7 % overall yield. This is the first bioinspired total synthesis of triarylmethanes natural products, and the approach used here may open up a new way for the synthesis of other triarylmethanes compounds.Chaper 2. The Studies on the Asymmetric Total Synthesis of RubromycinsIn this chaper, we firstly summarized the progress on the total synthesis of rubromycins. The main structural features of these compounds are: naphthoquione fragment and isocoumarin precursor are connected through a [5, 6] spiroketal skeleton. On the basis of our previous works toward the construction of [5, 6]-spiroketals, we designed a new route for the asymmetric total synthesis of rubromycins, and as a preliminary work, we firstly improved the synthetic protocols for the synthesis of the key fragments isocoumarin and naphthoquione. For isocoumarin fragment, we revised and improved the classical synthetic routes, and completed the synthesis of the precursor fragment 2-116 from 2-42 over 9 steps. The synthesis of naphthoquione fragment was a great challenge because of its electron-rich, high regioselective and highly oxidized properties. We accordingly designed a new route to synthesize the naphthalene fragment via a Danishefsky-type Diels-Alder reaction. Starting from 2-138, we successfully obtained the naphthoquinone diene precursor 2-134 through three steps of transformation. This method was more concise compared to the existing route for the synthesis of naphthoquione fragment.