Academic literature on the topic 'Conduramines'

Pour développer de nouveaux outils synthétiques, nous avons élaboré des variantes de la réaction de Petasis. L’utilisation des α-amino aldéhydes dans la réaction de Petasis a permis de synthétiser des diamines chirales avec une diastéréosélectivité totale. La réaction a donnée de bons résultats avec différents groupements protecteurs de l’amine (sulfonamide, carbamate, amide). Cependant au cours de la réaction, les amino aldéhydes s’épimérisent et l’excès énantiomérique des diamines préparées est donc faible (30%). La réaction de Petasis a été associée à la réaction de Diels-Alder dans un procédé domino pour aboutir à l’obtention de composés de type hexahydroisoindole. La réaction domino est complètement diastéréosélective et les molécules sont obtenues de manière énantiopure. Un second procédé domino, utilisant une réaction de métathèse croisée suivie d’une addition 1,4 intramoléculaire, a permis d’obtenir des composés possédant un motif morpholine de manière diastéréosélective. Une version intramoléculaire de la réaction de Petasis a été mise au point dans le but d’obtenir des carbocycles à six chainons. Cette réaction a permis de préparer la (+)-conduramine C-4 en peu d’étapes. La cyclisation a montré une diastéréosélectivité surprenante puisque la configuration entre l’amine nouvellement formée et l’alcool est trans. Cette configuration est opposée à celle obtenue dans la version intermoléculaire<br>To develop new synthetic tools, we developed variants of the Petasis reaction. The use of α-amino aldehydes in the Petasis reaction allowed to synthesize chiral diamines with a total diastereoselectivity. The reaction gave good results with different protective groups of the amine (sulfonamide, carbamate, amide). However, during the reaction, the amino aldehydes are epimerized and the enantiomeric excess of the prepared diamines is low (30%). The Petasis reaction was associated with the Diels-Alder reaction in a domino process to achieve the preparation of hexahydroisoindole type compounds. The domino reaction is completely diastereoselective and the molecules are obtained as enantiopure. A second domino process, using a cross-metathesis reaction followed by an intramolecular 1,4-addition, yielded compounds with a morpholine moiety in a diastereoselective manner. Intramolecular version of the Petasis reaction was developed in order to obtain carbon-six-membered rings. This reaction led to the preparation of (+)-conduramine C-4 in few steps. The cyclization has shown a surprising diastereoselectivity since the configuration between the newly formed amine and alcohol is trans. This configuration is opposite to the one obtained in the intermolecular versions

博士<br>國立中興大學<br>化學系所<br>98<br>英文摘要: Herein, we propose a novel, concise and flexible total synthesis of prominent and pioneer molecules belong to pseudo-carbasugar [COTC-Nap, (+)-MK7607] and aminocyclitol [(+)-Lycoricidine, (+)-Valienamine] families. Aforementioned compounds possess excellent biological activity such as antibiotic, antiviral, and glycosidase inhibitors and so on. Interestingly, all of our synthetic strategies utilized O-isopropylidene protected cyclohexenediol as key intermediate. Diastereoselective facile synthesis of key intermediate achieved from inexpensive L (or) D tartaric acid. First of all, sweetly, in pseudo carbasugar unit COTC-Nap synthesis, we utilized Baylis-Hilman reaction to introduce hydroxymethyl functional group at key intermediate, derived from D-Tartaric acid. Moreover we developed a new synthetic strategy in 8 steps with overall yield 4.4%. Similarly, our efforts in developing Heck carbonylation at L-Tartaric acid derived O-isopropylidene protected cyclohexenediol led to an efficient total synthesis of (+)-MK7607. in ten steps with an overall yield of 8.5%. Finally, we efficiently exploited the above mentioned flexible strategy to develop a new platform like 1,2-type and 1,4-type azido alcohol. Azido alcohols can easily prepare from L-Tartaric acid based key intermediate. In light of this, we furnished the short and simple total synthesis of (+)-Lycoricidine and (+)-Valienamine with high overall yield. Furthermore, this simple strategy also can readily be adopted for the synthesis of Conduramine A-1, Conduramine E and a key intermediate of (+)-pancratistatin.

博士<br>國立清華大學<br>化學系<br>97<br>The thesis concerns with the nitroso-Diels Alder (NDA) reactions of masked o-benzoquinones (MOBs) and application of this methodology to synthesize many kinds of conduramines. The thesis contain two major aspects : the first part concerned with the asymmetric nitroso-Diels-Alder (ANDA) reactions of MOBs and solving the hydrolyzing problem of NDA adducts. The second part applies the methodologies developed in the first part to furnish the syntheses of ent-conduramine A-1 tetraacetate, (+)-conduramine A-1, (+)-conduramine E-1 and (+)-ent-conduramine F-1. In the first chapter, we found ANDA reactions of MOBs with (+)-ketopinohydroxamic acid derived from (+)-camphorsulfonic acid shows the high yield and disastereoselectivities, the value of diastereomeric excess is up to 99 %. Interestingly, the major product is decided by the substituent on the MOB. With the evidences of ORTEP diagrams, we got the relationship between specific rotation and absolute configuration of these compounds. Furthermore, we solve the hydrolyzing problem of NDA adducts till we change the amino group to azide group, and we got a new rearrangement product. Utilizing the methodology of ANDA reactions of catechol has one MOM protection with (+)-ketopinohydroxamic and (-)-ketopinohydroxamic acid to furnish the syntheses of ent-conduramine A-1 tetraacetate and (+)-conduramine A-1, these are obtained from ten steps and eight steps separately. After getting the ANDA adduct from guaiacol and (+)-ketopinohydroxamic acid, we applied the methodology of new rearrangement developed in the first chapter to synthesize (+)-conduramine E-1 and (+)-ent-conduramine F-1 with ten steps and eight steps separately.

博士<br>國立中興大學<br>化學系所<br>100<br>Herein, we propose a facile and flexible synthetic strategy of chemically challenging and biologically important molecules from C2 symmetric inexpensive chiral pools [L (or) D Tartaric acid]. This expeditious total synthesis includes aminocyclitols [(+)-Valienamine & (+)-Valiolamine], pseudo-carbasugars [1-epi-(+)-MK7607, 1-epi-(-)-streptol], Conduramine series and (-)-Hygromycin A. Aforementioned compounds possess excellent biological activity, such as α- glucosidase inhibitors, antibiotics containing broad spectrum of activity such as peptidyl transferase inhibition activity and high hemaglutination inactivation activity and high antitreponemal activity. On the other hand, the key intermediate could serve as platform for many natural product syntheses. First of all, we utilized Wittig reaction to introduce methylene functional group in 9 steps total synthesis of (+)-Valienamine with 12.4% overall yield. Interestingly, a slightly deviated synthesis from the key intermediate led through asymmetric Sharpless dihydroxylation in 9 steps total synthesis of (+)-Valiolamine, with overall yield of 12.6%. In a concise strategy D-Tartaric acid transformed to Valienamine and Valiolamine. We applied the same procedure to synthesize the enantiomer of same intermediate from L-Tartaric acid and utilized a key step for Heck carbonylation to establish hydroxymethy functional precursor. We achieved an efficient total synthesis of 1-epi-(+)-MK7607 and 1-epi-(-)-streptol in 9 steps with overall yield 11.2% and 12.1% respectively. Similarly, our efforts in devising, simple and flexible strategy to provide an efficient and enantiospecific approach to Hygromycin A. We developed a new platform like 1,4-type azido alcohol aminocyclitol fragment and synthesized through 1,3-transposition from enantiomer L-Tartaric acid. Furanoside fragment was synthesized from different starting materials like D-Tartaric acid or D-Arabinose with short steps and in high yield. Coupling reaction of all key fragments channeled us to complete formal total synthesis of Hygromycin A in 11 steps with overall yield 14.6%. Finally, we efficiently exploited the above mentioned flexible strategy to develop O-isopropylidene protected allylic epoxide, derived from L-Tartaric acid. Other than double bond, diverse stereochemistry of four functional groups in six membered rings achieved from different steps lead rapid high yield synthesis of eight conduramines as its tetraacetates. We achieved total synthesis of Conduramine A-1 and E in 5 steps with overall yield of 30.5% and 36.9% respectively. In addition, Conduramine B-1, C-1 and C-4 were accomplished in 7 steps with overall yield 32.7%, 25.2% and 11.7% respectively. Moreover, we synthesized Conduramine D-1 in 9 steps with overall yield 13.8%. In a similar way, ent-Conduramine F-1 and ent-Conduramine F-4 were completed in 6 steps with overall yield 31.7% and 33.1% respectively. Finally, we also utilized the intermediate for the synthesis of inositol analogues in 8 steps with total yield of 25.2%.