Stereochemical challenges in characterizing nitrogenous spiro-axane sesquiterpenes from the Indo-Pacific sponges Amorphinopsis and Axinyssa

Abstract

An investigation was conducted to identify the structures and bioactive properties of five compounds isolated from the Halichondrida sponges Amorphinopsis foetida and Axinyssa aplysinoides. All compounds possessed the spiro-axane sesquiterepene core and all were substituted at C-2 with nitrogen containing functionality. The stereochemistry of one known compound has been revised to (2R,5R,10S)-2-formamido-6-axene (3). It exhibited mild selective solid tumor and mild antibacterial activity and was found from Axinyssa. A second known substance whose stereochemistry has also been revised, (2R,5R,10S)-2-isothiocyanato-6-axene (4) plus its undescribed diastereomer (5) were isolated from Amorphinopsis. Both sponges were the source of two new N-phenethyl-2-formamido-6-axene diastereomeric compounds (6) and (7). No solid tumor or antibacterial activity was found for 4 -7.

Marine Isonitriles and Their Related Compounds

“…However, they identified the relative configuration of the both compounds as (2 R ,5 R ,10 R ) with a stereochemistry at C-10 unusual for natural products. Wegerski et al revised the configuration from (2 R ,5 R ,10 R )- to (2 R ,5 R ,10 S )-2-isothiocyanato-6-axene ( Sp15 ) and (2 R ,5 R ,10 S )-2-formamido-6-axene ( Sp16 ) [ 63 ]. During their investigations, the group also found the isothiocyanate Sp17 with (2 S ,5 R ,10 S )- or (2 R ,5 S ,10 S )-configuration [ 63 ].…”

“…Wegerski et al revised the configuration from (2 R ,5 R ,10 R )- to (2 R ,5 R ,10 S )-2-isothiocyanato-6-axene ( Sp15 ) and (2 R ,5 R ,10 S )-2-formamido-6-axene ( Sp16 ) [ 63 ]. During their investigations, the group also found the isothiocyanate Sp17 with (2 S ,5 R ,10 S )- or (2 R ,5 S ,10 S )-configuration [ 63 ]. Furthermore they found in analogy to halichonadin J ( Eu30 ), vide supra the compounds N -phenethyl-2-formamido-6-axene ( Sp18 ) with either (2 S ,5 S ,10 S ) or (2 R ,5 R ,10 S ) configuration and N -phenethyl-2-formamido-6-axene ( Sp19 ) with either (2 S ,5 R ,10 S ) or (2 R ,5 S ,10 S ) configuration [ 63 ].…”

Marine natural products

“…448, 449 The relative stereochemistry of 377 has been revised to (2R*,5R*,10S*). 449 In the same report, a specimen of Amorphinopsis foetida (Papua New Guinea) was also found to contain 375 and 376 along with 378 and the previously reported 379 (Amorphinopsis (syn. Trachyopsis) aplysinoides).…”

Natural sesquiterpenoids

“…The first sponge also contains the known metabolite 327, whose stereochemistry has now been revised, whilst the second contains the spiroaxene 328, whose stereochemistry has also been corrected, and its new diastereomer 329. 314 Another compound of this type, 3-oxo-axisonitrile-3 330, has been found in a Chinese sponge of the Acanthella genus. 315…”