Kallolide A acetate pyrazoline

In the crystal structure of kallolide A acetate pyrazoline [systematic name: 7-methyl-16-oxo-4,10-bis(prop-1-en-2-yl)-17,18-dioxa-14,15-diazatetracyclo[9.4.2.16,9.01,12]octadeca-6,8,14-trien-5-yl acetate], C23H28N2O5, there is a 12-membered carbon macrocyclic structure. In addition, there is a trisubstituted furan ring, an approximately planar γ-lactone ring [maximum deviation of 0.057 (3) Å] and a pyrazoline ring, the latter in an envelope conformation. The pyrazoline and the γ-lactone rings are fused in a cis configuration. In the crystal, molecules are linked by weak C—H⋯O interactions, forming a two-dimensional network parallel to (001). An intramolecular C—H⋯O hydrogen bond is also present.


Comment
The title compound, in its enantiopure form, was prepared from the known pseudopterane diterpene kallolide A acetate, which was isolated from the marine sea plume Pseudoptereogorgia kallos.
The gorgonian octocorals of the genus Pseudopterogorgia are common inhabitants of tropical West Indies (Humman, 1996) and Indo-Pacific reefs. They can be adapted to different marine reef environments, from shallow to clear deep waters.
Twenty two species and subspecies of Pseudopterogorgia have been reported and are commonly known as sea plumes for the feather-like appearance of their branches and ramifications (Bayer, 1961;Marrero et al., 2010). Despite these general morphological similarities each species can be identified by differences in color, branch ramification, polyps size, texture, growth form, mucus production, sclerites, spicule, and geographical distribution (Yoshioka, 1997;Sánchez et al., 2003;Sánchez & Lasker, 2003). In the West Indies region, sea plumes from this genus are commonly found from Bermuda to the Bahamas, the Florida Keys, the Greater and Lesser Antilles, and the northern coast of South America to Brazil (Bayer, 1961;Williams & Vennam, 2001;Lasker & Coffroth, 1983;Sánchez et al., 1998). West Indies Pseudopterogorgia species are well known for the production of a variety of diterpenoids of fascinating molecular structures (Marrero et al., 2010) that exhibit a wide spectrum of biological activities including antibacterial, anti-inflammatory, antimalarial, and cytotoxic properties (Heckrodt & Mulzer, 2005). An early investigation on the chemical composition of Pseudopterogorgia kallos showed that it is a rich source of pseudopterane-type diterpenoids (Look et al., 1985). However, during the last eight years (2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011) subsequent chemical scrutiny has demonstrated that this gorgonian species also contains a number of minor bioactive diterpenes that are based on distinctively novel carbon frameworks (i.e., bielschowskysin, ciereszkolide, intricarene, kallosin A, and providencin) (Marrero et al., 2003a;Marrero et al., 2003b;Marrero et al., 2004a;Marrero et al., 2004b;Marrero et al., 2005).
The molecular structure of kallolide A acetate pyrazoline is shown in Fig. 1. It has a twelve carbon-membered macrocyclic structure with three additional rings: a trisubstituted furan, an approximately planar γ-lactone ring twisted on the C9-C10 bond, and a pyrazoline ring in an envelope conformation with C9 as the flap atom. Fused in a cis configuration, the angle between the mean planes of the pyrazoline and the γ-lactone rings is 111.5 (1)°.
In the crystal structure ( Fig. 3), molecules are linked via C8-H8···O5 and C9-H9···O4 hydrogen bonds, forming a two-dimensional network. An additional intramolecular C16-H16A···O5 hydrogen bond is also present. The absolute structure was assigned as (1S, 2S, 7R, 8R, 9R, 10S), based on previous asymmetric synthesis of kallolide A and kallolide A acetate (Marshall & Liao,1998). Department of the University of Puerto Rico, Río Piedras Campus. The organism was partially air-dried, frozen, and lyophilized prior to its extraction. The dry specimens (1.07 kg) were blended using a mixture of CH 2 Cl 2 /MeOH (1:1) (20 x 1 L). After filtration, the crude extract was concentrated and stored under vacuum to yield a greenish gum (166 g). The crude extract was suspended in water (2 L) and extracted with n-hexane (3 x 2 L), CHCl 3 (3 x 2 L), and EtOAc (2 x 2 L). Each extract was concentrated under reduced pressure to yield 71.9 g of the n-hexane extract (PkH), 39.3 g of the CHCl 3 extract (PkC), and 1.47 g of the EtOAc extract (PkA). The isolation and purification of the starting material, kallolide A acetate, for the synthesis of the title compound was achieved via published procedures [Marrero et al. (2006)]. A CHCl 3 solution of kallolide A acetate (15 mg) was treated with an excess of CH 2 N 2 ether solution and stirred at room temperature. After 36 h the reaction mixture was concentrated in vacuo to remove the ether solution of CH 2 N 2 to yield 16.7 mg of kallolide A acetate pyrazoline as a pure colorless solid (16.7 mg, 100% yield). The title compound was recrystallized by slow evaporation using hot acetone as a solvent.