Search

A 62-year-old woman was diagnosed with autoimmune hemolytic anemia (AIHA), with cytology- and culture-negative pleural effusion. AIHA did not improve with steroid therapy. Computerized tomography (CT) detected a left ovarian tumor, which was resected surgically, and AIHA improved temporarily. Pathological examination yielded a diagnosis of diffuse large B-cell lymphoma (DLBCL). Positron emission tomography with CT suggested systemic infiltration of lymphoma. Rituximab-containing chemotherapy (R-CHOP regimen) yielded rapid decreases in lymphoma lesions and pleural effusion with improvement of AIHA. After six courses of R-CHOP, complete response (CR) was confirmed and AIHA remitted completely. Two months after confirmation of CR, however, lymphoma and AIHA relapsed simultaneously. To our knowledge, this is the first case report describing ovarian DLBCL preceded by AIHA.

Rhopaloic acid A (+)-1 and the related compounds (–)-ent-1 and (±)-rac-1 have been stereoselectively synthesized. The synthetic strategy consists of successive homologation of (2E,6E)-farnesol 7 and cyclization to form a tetrahydropyran ring, together with final introduction of an α-methylene group on the carboxylic moiety. The cyclization is carried out by intramolecular hetero-Michael addition leading to 2,5-disubstituted tetrahydropyrans. The stereochemistry can be rationalized by invoking a model of a chair-like transition state. The asymmetric synthesis is achieved by way of the Evans’ asymmetric alkylation procedure using (S)- or (R)-4-benzyloxazolidin-2-one as the chiral auxiliary. In the event, the configuration of natural rhopaloic acid A (+)-1 could be assigned as 2R,5S by comparison of the specific rotations of synthetic compounds with that of the natural product.

The stereoselective synthesis of rac- and ent-rhopaloic acid A 1 has been accomplished, via successive homologation of (2E,6E)-farnesol 2 and cyclization to form a tetrahydropyran ring, together with final introduction of an α-methylene group; the asymmetric synthesis was achieved via an Evans’ asymmetric alkylation using (S)-4-benzyloxazolidin-2-one as a chiral auxiliary; the synthetic rhopaloic acid A, with a predicted absolute configuration of (2S,5R), had a specific rotation of opposite sign to that of the natural product, and therefore the configuration of natural rhopaloic acid A should be assigned as (2R,5S).

Rhopaloic acid A (+)-1 and the related compounds (–)-ent-1 and (±)-rac-1 have been stereoselectively synthesized. The synthetic strategy consists of successive homologation of (2E,6E)-farnesol 7 and cyclization to form a tetrahydropyran ring, together with final introduction of an α-methylene group on the carboxylic moiety. The cyclization is carried out by intramolecular hetero-Michael addition leading to 2,5-disubstituted tetrahydropyrans. The stereochemistry can be rationalized by invoking a model of a chair-like transition state. The asymmetric synthesis is achieved by way of the Evans’ asymmetric alkylation procedure using (S)- or (R)-4-benzyloxazolidin-2-one as the chiral auxiliary. In the event, the configuration of natural rhopaloic acid A (+)-1 could be assigned as 2R,5S by comparison of the specific rotations of synthetic compounds with that of the natural product.

Ring-expansion of methyl 2-bromomethyl-5-oxiranylpent-2-enoate (7) with various acids was studied; treatment with Lewis acids (TiBr4, MgBr2 and ZnBr2) afforded the tetrahydrofuran derivative 4-Br as a major product, while reaction with silver salt (AgNO3/KPF6), which is known to have a high halide affinity, gave preferentially the tetrahydropyran 3-ONO2 derivatives as the major products.

Ring-expansion of methyl 2-bromomethyl-5-oxiranylpent-2-enoate (7) with various acids was studied; treatment with Lewis acids (TiBr4, MgBr2 and ZnBr2) afforded the tetrahydrofuran derivative 4-Br as a major product, while reaction with silver salt (AgNO3/KPF6), which is known to have a high halide affinity, gave preferentially the tetrahydropyran 3-ONO2 derivatives as the major products.

In order to construct the tetrahydropyran ring of rhopaloic acid A and hippospongic acid A, the ring-expansion of methyl 2-bromomethyl-6,7-epoxyhept-2-enoate with various acids was studied; treatment of the bromo oxirane with Lewis acids (TiBr 4 , MgBr 2 and ZnBr 2 ) afforded a tetrahydrofuran derivative as the major product, while reaction of the oxirane with silver salt (AgNO 3 /KPF 6 ) gave a tetrahydropyran derivative as the major product.

The stereoselective synthesis of rac- and ent-rhopaloic acid A 1 has been accomplished, via successive homologation of (2E,6E)-farnesol 2 and cyclization to form a tetrahydropyran ring, together with final introduction of an α-methylene group; the asymmetric synthesis was achieved via an Evans’ asymmetric alkylation using (S)-4-benzyloxazolidin-2-one as a chiral auxiliary; the synthetic rhopaloic acid A, with a predicted absolute configuration of (2S,5R), had a specific rotation of opposite sign to that of the natural product, and therefore the configuration of natural rhopaloic acid A should be assigned as (2R,5S).