I mentioned the team-of-Sherpas approach to making molecules, but that's something that (fortunately) I haven't had to do much in recent years. In drug discovery, we try to avoid anything involving that kind of chemical labor - the rest of the drug development stuff is enough to keep everyone busy, thanks. Contrast that to some academic organic chemistry, where molecules that need pyramid-construction-size teams are sometimes the whole point.

I did big-molecule natural product synthesis for my PhD, and I don't miss it for a minute. (I don't miss a lot of things about my PhD for a minute, for that matter, but that's another story.) It's a specialized world inside organic chemistry, which during its glory days was for many the only world that mattered. It's hard to put exact dates on that, but you could start in the 1950s, end sometime in the late 70s or early 80s, and not set off too many arguments.

It's not that huge and difficult molecules aren't made any more. They are, and some of them are weird enough to have made the old titans like R. B. Woodward choke on their Scotch. But it's different somehow; I think it's because we've gotten a little too good. There are a lot of reactions we can pull out now that Woodward's generation never lived long enough to see, reactions that do things they never knew could be done. So now, when some massive team of postdocs makes Voodoomycin, Whateverol, or some other molecule that looks like your structure-drawing program malfunctioned all over the page, it doesn't set off the awe that the older syntheses did. It can't. There are dozens, hundreds, thousands of people who look at the resulting paper and say "Hey, give me a team of fifty smart, highly trained workaholics and a million dollars from NIH, and I'll make Whateverol, too."

We can make almost anything (given enough sweat, time, and money,) but most complex molecules still use up far too much of all three. It's not the boundries of the science that hold us back any more, just the boundries of the real world. Those who aren't well acquainted with the field figure it can do most anything, but those inside it know, for practical reasons, that we often can't.