N-3′-ethylaplysinopsin and related alkaloids

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N-3′-ethylaplysinopsin and related alkaloids

Postby sage-borodin » Sun May 14, 2017 9:35 am

Smenospongia aurea is a fascinating marine organism which produces a fascinating array of indole alkaloids, all with many potentials.

6-bromo-2'-de-N-methylaplysinopsin and N-3′-ethylaplysinopsin particularly piqued my interest.

A new indole alkaloid, N-3′-ethylaplysinopsin (68), isolated from the Jamaican sponge Smenospongia aurea, was shown to potently bind to the human serotonin 5-HT2C receptor subtype expressed in a mammalian cell line (Hu et al., 2002). The authors suggest that the R2 functional groups at position 2′ may play an important role in regulating subtype selective binding to the 5-HT2C receptor, a receptor found in high density in the choroid plexus, the site of cerebrospinal fluid production.

The high affinity for agonism at 5HT2a and 5HT2c receptor subtypes displayed by some of these compounds particularly caught my attention.

Other research outlining Smenospongia aurea and the compounds which it produces:
New antiinfective and human 5-HT2 receptor binding natural and semisynthetic compounds from the Jamaican sponge Smenospongia aurea.
In addition to the sesquiterpene-phenol aureols (1), 6'-chloroaureol (2), and aureol acetate (3), eight indole alkaloids including the new N-3'-ethylaplysinopsin (9) have been isolated from the Jamaican sponge Smenospongia aurea. Makaluvamine O (10), a new member of the pyrroloiminoquinone class, was also isolated. The structures were characterized by spectroscopic methods, and two new derivatives of aureol were prepared to optimize the biological activity. Aureol N,N-dimethyl thiocarbamate (1a) and 6-bromoaplysinopsin (7) exhibit significant antimalarial and antimycobacterial activity in vitro. Compound 6 showed activity against the Plasmodium enzyme plasmepsin II. The 6-bromo-2'-de-N-methylaplysinopsin (6), 6-bromoaplysinopsin (7), and N-3'-ethylaplysinopsin (9) displaced high-affinity [(3)H]antagonist ligands from cloned human serotonin 5-HT(2) receptor subtypes, whereas the other compounds tested did not. Remarkably, the 6-bromo-2'-de-N-methylaplysinopsin (6) showed a > 40-fold selectivity for the 5-HT(2C) subtype over the 5-HT(2A) subtype.

Here some of the potential functions of these compounds are outlined:
Marine monoindole alkaloids, sharing structure similarities with serotonin, are certain to become useful tools to facilitate the understanding of serotonin receptor function and generate new drug leads for the treatment of depression, anxiety, migraines and other 5HT receptor related disorders

The structural similarity of indole alkaloids to endogenous amines and neurotransmitters has led researchers to postulate the possible neurological activity of these molecules. Several compounds carrying an indole moiety have been reported to possess affinity towards different serotonin receptors: barettin, 8,9-dihydrobarettin,13 tris-indole alkaloids gelliusine A and B,14 and σ-conotoxin.15 Methylaplysinopsin (1) (Fig. 2) isolated from Aplysinopsis reticulata by Baird-Lambert et al. was reported to inhibit monoamine oxidase (MAO) and to displace serotonin from its receptors.16 Other molecules from this group: 6-bromo-2′-de-N-methylaplysinopsin (2), 6-bromoaplysinopsin (3), and N-3′-ethylaplysinopsin (4) (Fig. 2) isolated from Smenospongia aurea were reported to displace high-affinity antagonist binding for human 5-HT2C and 5-HT2A receptors.17 N-3′-ethylaplysinopsin did not display selectivity to either of these two receptors (Ki of 3.5 μM and 1.7 μM for 5HT2C and 5HT2A receptor, respectively). 6-Bromoaplysinopsin showed only low selectivity towards 5HT2C receptors (Ki 0.33 μM and 2.0 μM for 5HT2C and 5HT2A receptor, respectively); however 6-bromo-2′-de-N-methylaplysinopsin exhibited strong (40 fold) selectivity to 5HT2C receptors (Ki 2.3 μM for 5HT2C and >100 μM for 5HT2A). Besides neurological activity, 6-bromoaplysinopsin also showed significant activity against Plasmodium falciparum.

5,6-dibromo-N,N-dimethyltryptamine (5)18 and 5-bromo-N,N-dimethyltryptamine (6)19 (Fig. 3) exhibited antimicrobial activity as reported by Tymiak.20 The dibrominated compound was significantly more active over the monobromotryptamine. Both of the compounds were also found to possess neurological activity: 5,6-dibromo-N,N-dimethyltryptamine showed antidepressant action in forced swim test and tail suspension test;21,22 5-bromo-N,N-dimethyltryptamine exhibited strong sedative effect in the locomotor activity test.


Smenospongia aurea is a fascinating organism, it is also the natural source of a known psychedelic brominated tryptamine compound, namely 5-bromo-N,N-Dimethyltryptamine.

Here, in TIHKAL, shulgin comments on these brominated marine tryptamines:
The compound with a methoxy group substituent at the 1-position is called Lespedamine, 1-MeO-DMT. With an NO bond, this should be classified as a substituted hydroxylamine. I would love to know if anyone anywhere has ever tried smoking it. I suspect it might very well be active, but it is, to my knowledge, untried. I wonder why it deserves a trivial name, vis., Lespedamine? Two additional ring-substituted derivatives of DMT come from the marine world. 5-Bromo-DMT and 5,6-dibromo-DMT are found in the sponges Smenospongia auria and S. echina resp. I have no idea if they are active by smoking (the 5-Br-DMT just might be) but they are quantitatively reduced to DMT by stirring under hydrogen in methanol, in the presence of palladium on charcoal. A very closely related sponge, Polyfibrospongia maynardii, contains the very closely related 5,6-dibromotryptamine and the corresponding monomethyl NMT. I had the fantasy of trying to scotch the rumor I'm about to start, that all the hippies of the San Francisco Bay Area were heading to the Caribbean with packets of Zig-Zag papers, to hit the sponge trade with a psychedelic fervor. This is not true. I refuse to take credit for this myth.

First, on an unrelated note 1-MeO-DMT was given the name Lespedamine is named as such due to its occurrence in the Lespedeza bicolor plant.
Second, in relation to the following TIHKAL excerpt: 5-Bromo-DMT and 5,6-dibromo-DMT are found in the sponges Smenospongia auria and S. echina resp. I have no idea if they are active by smoking (the 5-Br-DMT just might be). The activity of 5-bromo-DMT has been anecdotally confirmed, a pseudonymous chemist calling himself "doctor osculum" sent a message to vice media reporter Hamilton Morris describing the synthesis and qualitative effects produced by 5-Br-DMT, this is outlined in the following link. https://www.vice.com/en_us/article/sea-dmt-000481-v20n3

I apologize for the "thrown together" and hectic format of this post, it's a complex area of research with many facets and intricacies, and in my enthusiasm for the matter I often "jump around" or provide disorganized information while trying to include every detail in a single post. I am also aware that I left out quite a bit, but it is a starting point, which should be further refined and organized over time.
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