Plants - Drugs Mind - Spirit Freedom - Law Arts - Culture Library  
Donations are Matched During Erowid's
Annual Public Support Drive!
September is our annual support drive, when we ask YOU to support reliable, independent drug information by helping Erowid reach more unique
donations than ever before in a single month (1,225 is the goal this year).
We still need 658 donations ($5+) by September 30th. [see progress]

Donate by Bitcoin
From: (Sam Knight)
Newsgroups: alt.psychoactives
Subject: Re: LSD analogues (was re: ALD-52)
Date: 3 Oct 1994 12:33:28 GMT
Message-ID: <36otmo$>

Christopher Hemming ( wrote:
: While we're on the subject of LSD analogues, I understand that replacing
: the methyl group on nitrogen 6 with ethyl, allyl or propyl results in 
: compounds of similar, or even higher (by a factor of 2-3) potency.  Is
: this right?  I'm pretty sure I've actually looked up the paper, but of
: course it was just a glance at it.  So, is that right?

I have seen that too. The reference was posted along with a reference to
the JACS article on sythesis of lysergic acid methyl ester from L-tryptophan
and some article on the synthesis of LSD from LSA using POCl3.
I think the post is available for FTP.

: I find it interesting that the LSD molecule is so sensitive to substitution.
: There aren't many substitutions that will retain activity (just a couple
: of types, as compared with the psychedelic phenethylamine family where you
: can do just tons of stuff).  It must be fitting into that receptor pocket
: really nicely.  Especially the diethylamine group.  I understand just 
: about any other substitution pattern there pretty much abolishes activity.
: Hmm.  I wonder if you replaced some of the -H's on those two ethyl groups
: with -F's...  That would keep the size about the same, but would change the
: charge distribution.  Has it been tried?  -F for -H is supposed to be a
: fun substitution in bioactive molecules, often modifying activity since 
: it's the same size (roughly) as -H, but is a lot harder for enzymes to 
: take off.  Apparently monofluoroacetic acid is one of the most generally
: toxic substances known (i.e. bad for most life forms) because it gets into
: some important pathway (related to carbon oxidation,  Kreb's cycle?) and
: totally fucks it all to hell.

There are other LS amides that _are_ active at dosages less than 20x that of
LSD including ALD-52, d-LS morpholide (20% LSD activity), 1-N-methyl LSD
(40% activity), d-LS dimethylamide (10%), d-LS ethylamide (5%) and
d-(1-N-methyl-LS-pyrrolidide) (7%)
I think research into fluroLSDs has been a bit limited (I certainly
havent seen any in my wandering, and it being a fairly notorious
sheduled drug must put a bit of a damper on human trials..)
It is, however, a good idea..
Does anyone have information on the breakdown path of LSD, I think
it is metabolised by MAO. Certainly MAOIs increase LSD potency.

: Also, -Cl lies somewhere between -H and -CH3 in size (or so I'm told) so 
: making of the ethyl groups a 2-chloroethyl group wouldn't be quite as 
: bad size-wise as making it a propyl group (which apparently abolishes 
: activity).  Of course, 2-chloroethyl ethyl amine would polymerize/cyclize 
: nicely.  Maybe it wouldn't be too easy to work with, so a different 

sure looks that way..

: synthesis might be required rather than just using a different amine in
: the amidation step.  But I don't really know what I'm talking about, I'm
: just throwing out ideas.

you and me both :)

: ------------------------------------------------------------------------------
:                              Waterloo, Ont.
:   Better living through chemistry -- For every problem, a chemical solution.
: ------------------------------------------------------------------------------